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Research Description

Our lab studies (a) the regulation of DNA replication in normal and cancer cells using genetics and genomics, (b) the DNA damage response of a mammalian cell and (c) the role of small RNAs (including microRNAs) in control of cell proliferation.How DNA replication is initiated in human cells, and how dysregulation of this process leads to the genomic instability seen in cancers has been a major theme of research over the last two decades. We are also interested in how tumor suppressor genes and chromatin remodeling factors co-ordinate the response of a cell to DNA damage to prevent the appearance of mutations in the progeny. Finally, we are exploring the role of microRNAs in cell-cycle regulation with an emphasis on microRNAs that inhibit cell proliferation.

Following are some references for the research being conducted in our lab according to the area of research.

GENOMICS

The ENCODE program is the post-genomics program initiated by National Human Genome Research Institute to annotate the human genome. We use genome tiling microarrays to determine origins of replication, replication profile, replication factor binding sites and epigenetics of the human genome. Obviously the next step will be to see how these are changed in cancers. (http://genome.bioch.virginia.edu/encode)


 CANCER GENOMIC INSTABILITY

that stems from an imbalance of replication factors


RESPONSE TO DNA DAMAGE

that stems from abnormalities of DNA replication or from external agents such as chemotherapeutic agents or radiation. The response pathways often use tumor suppressor proteins like p53, Fanconi Anemia complex or BRCA1. A related area of research focuses on two putative AAA+ ATPases (Rvb1 and 2) that are part of the TIP60 chromatin-remodeling complex that responds to DNA damage.


DETECTING GENOMIC INSTABILITY

in cell lines and cancers by ultra highthroughput DNA sequencing.


MICRO-RNAs

We are examining how the new "dark matter" of the genome, microRNAs and newly discovered non-micro-short RNAs, regulate cell proliferation and differentiation in muscle differentiation and in prostate cancer cells.


Lab Members

Principal Investigator

Anindya Dutta

Associate Professor

Dr. Amir Jazaeri (Department of Obstetrics and Gynecology)

Research Associates

Yoshiyuki Shibata Ph.D., Kyushu University, Fukuoka
Etsuko Shibata Ph.D., Nagasaki University, Nagasaki
Bijan Dey Ph.D., McMaster University, Canada
Masamitsu Negishi MD, Ph.D., Juntendo University
Ashraf Dar Ph.D., JNU, New Delhi
Kyung Yong Lee Ph.D., Seoul National University
Jun Sub Im Seoul National University
Kouhei Sakurai DDS, Ph.D., U. of Tokyo
 

Postdoctoral Fellows

Pankaj Kumar Ph.D., CDFD, Hyderabad
Laura Dillon Ph.D., Wake Forest University
 

Graduate Students

Adam Mueller MD, Ph.D. student, Biochemistry
Charles Preston Goforth Ph.D. student, Biochemistry
Magdalena Wegrzynska Ph.D. student, Biochemistry
Brian Reon MD, Ph.D. student, Pathology
 

Undergraduate Students

Nicholas Lee UVa
Debbie Pan UVa
Eric Teplitz UVa

Staff

Nancy Rush

Alumni

Junjie Chen Professor, M.D. Anderson Medical Center
Ellen Winchester Software engineer, Broad Institute, M.I.T
Partha Saha Sr. Lecturer, Saha Institute, Kolkata
Suman K. Dhar Professor, JNU, New Delhi
Zophonias Jonsson Sr. Lecturer, University of Iceland
David Garcia Quintana Assoc. Professor, Autonomous University, Barcelona
Chinweike Ukomadu Asst. Professor, Harvard Medical School
Yi Ling Lin Asst. Professor, UCLA
James Wohlschlegel Asst. Professor, UCLA
Sandeep Saxena Asst. Professor, National Institute of Immunology, New Delhi
Takeshi Senga Assoc. Professor, Nagoya University
Kenichi Yoshida Assoc. Professor, Meiji University
Yuefeng Chen Research Assistant, Eli Lilly, Indianapolis
Uma Sivaprasad Research Asst. Professor, U. of Cincinnati
Yuichi J. Machida Asst. Professor, Mayo Clinic, Rochester
Christopher Taylor Assoc. Professor, LSU Health, New Orleans
Yong Sun Lee Asst. Professor, University of Texas Medical Branch, Galveston
Wenge Zhu Asst. Professor, George Washington University
David Takeda Oncology Fellow, Dana Farber Cancer Institute
Jamie Teer Asst. Member, Moffitt Cancer Center
Ankit Malhotra Assoc. Computational Scientist, Jackson Laboratory for Genomic Medicine, CT
Kenta Terai Asst. Prof., U. of Tokyo
Sudhakar Jha Asst. Prof. Centre for Translational Medicine, National University Singapore
Mignon Keaton Director of Project Management and Scientific Administration, Center of Human Genome Variation, Duke University
Neerja Karnani PI, Singapore Institute of Clinical Sciences
Jie Lin Senior Research Technologist, St. Jude Children's Research Hospital, Memphis, TN
Ryan Layer Ph.D. student, UVA
Tarek Abbas Asst. Prof., University of Virginia
Jeffrey Gagan Ph.D., M.D. part of MSTP, U. of Virginia
Dandan Sun CBPartners, New York
Jonghoon Park Scientist, LG Life Sciences, Daejon
Ashish Gupta Asst. Professor, Shiv Nadar University (SNU), Greater Noida, U.P

Undergraduate alumni

Name Undergraduate U. Current position
Phillip Pian Harvard Fellow, Anesthesiology, MGH
Patrick Lee Harvard Physician
Nikhil Wagle Harvard Instructor, Oncology, Dana Farber
Tara Marathe Colby -
Neal Mitra Yale Consultant, EMD Serono
Daniel Kim UVA Research Asst., Industry
Somsakul Wongpalee UVA Ph.D. student, UCLA
Eric Voll UVA Ph.D. student, Northwestern
Michael Billett UVA MD student, UVA
David Wu First in Distinguished Majors Symposium UVA NIH
Suraj Mishra UVA NIH

Publications

A. Original Articles in Refereed Journals

  1. Dutta A, Wang L-H, Hanafusa T, Hanafusa H. Partial nucleotide sequence of Rous sarcoma virus-29 provides evidence that the original Rous sarcoma virus was replication defective. J Virol. 1985; 55, 728-735.

  2. Dutta A, Majumder H K. Effects of monosaccharides on uptake of Leishmania donovani promastigotes by murine macrophages. Indian Jl Biochem Biophys. 1986; 23, 1-4.

  3. Dutta A, Dorai T, Hanafusa H. The putative trans-activator in the MA gag region of Rous sarcoma virus is not required for cell transformation. J Virol. 1988; 62, 4767-4769.

  4. Prywes R, Dutta A, Cromlish J A, Roeder R G. Phosphorylation of serum response factor, a factor that binds to the serum response element upstream of the c-fos promoter. Proc Natl Acad Sci USA. 1988; 85, 7206-7210.

  5. Dutta A, Stoeckle M Y, Hanafusa H. Serum and v-src increase the level of CCAAT binding factor required for transcription from a retroviral LTR. Genes & Dev. 1990; 4, 243-254.

  6. Dutta A, Hamaguchi M, Hanafusa H. Serum independence of transcription from the promoter of an avian retrovirus in v-src transformed cells is a primary, intracellular effect of increased tyrosine phosphorylation. Proc Natl Acad Sci U S A. 1990; 87, 608-612.

  7. Dutta A, Stillman B. cdc2 family kinases phosphorylate a human cell DNA replication factor, RPA, and activate DNA replication. EMBO J. 1992; 11, 2189-2199.

  8. Dutta A, Ruppert J M, Aster J C, Winchester E. Inhibition of DNA replication factor RPA by p53. Nature. 1993; 365, 79-82. (Accompanied by News and Views piece in Nature)

  9. Chen J, Jackson P K, Kirschner M W, and Dutta A. Separate domains of p21 involved in the inhibition of cdk kinase and PCNA. Nature. 1995; 374, 386-388

  10. Dutta A, Chandra R, Leiter L M, Lester S. Cyclins as markers of tumor proliferation and angiogenesis: immunocytochemical studies in breast cancer. Proc Natl Acad Sci USA. 1995; 92, 5386-5390.

  11. Keshav K F, Chen C, Dutta A. Rpa4, a homolog of the 34 kDa subunit of the replication protein A complex. Mol. Cell. Biol. 1995; 15, 3119-3128.

  12. Chen J, Peters R, Saha P, Lee P, Theodoras A, Pagano M, Wagner G, Dutta A. A 39 amino acid fragment of the cell cycle regulator p21 is sufficient to bind PCNA and partially inhibit DNA replication in vivo. Nucleic Acids Research. 1996; 24, 1727-1733.

  13. Lin Y-L, Chen C, Keshav K F, Winchester E, Dutta A. Dissection of functional domains of the human DNA replication protein complex Replication Protein A. J. Biol. Chemistry. 1996; 271, 17190-17198.

  14. Leiter L M, Chen J, Marathe T, Tanaka M, Dutta A. Loss of transactivation and transrepression function, and not RPA binding, alters growth suppression by p53. Oncogene. 1996; 12, 2661-2668.

  15. Henricksen L A, Carter T, Dutta A, Wold M S. Phosphorylation of human replication protein A by the DNA-dependent protein kinase is involved in the modulation of DNA replication. Nucleic Acids Research. 1996; 24, 3107-3112.

  16. Chen J, Saha P, Kornbluth S, Dynlacht B, Dutta A. Cyclin binding motifs are essential for the function of p21/CIP1. Mol. Cell. Biol. 1996; 16, 4673-4682.

  17. Mashal R D, Lester S, Corless C, Richie J P, Chandra R, Propert K J, Dutta A. Expression of cell-cycle regulated proteins in prostate cancer. Cancer Research. 1996; 56, 4159-4163.

  18. Chen J, Chen S, Saha P and Dutta A. p21 disrupts the recruitment of human Fen1 by proliferating cell nuclear antigen into the DNA replication apparatus. Proc. Natl. Acad. Sci. USA. 1996; 93, 11597-11602.

  19. Saha P, Eichbaum Q, Silberman E D, Mayer B J, Dutta A. p21/CIP1 and Cdc25A, competition between an inhibitor and an activator of cyclin dependent kinases. Mol. Cell. Biol. 1997; 17, 4338-4345.

  20. Quintana DG, Hou ZH, Thome KC, Hendricks M, Saha P, Dutta A. Identification of a novel subunit of the human origin recognition complex with homology to yeast Orc4. J. Biol. Chemistry 1997; 272, 28247-28251.

  21. Lin Y L, Shivji M K K, Chen C, Kolodner R, Wood R D, Dutta A. The evolutionarily conserved zinc finger motif in the largest sub-unit of human RPA is required for DNA replication and mismatch repair but not for nucleotide excision repair. J. Biol. Chemistry 1998; 273, 1453-1461.

  22. Saha P, Chen J, Thome K C, Lawlis S J, Hou Z H, Hendricks M, Parvin J D, Dutta A. The human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase. Mol. Cell. Biol. 1998; 18, 2758-2767.

  23. Saha P, Thome K C, Yamaguchi R, Hou Z H., Weremowicz S and Dutta A. The human homolog of Saccharomyces cerevisiae CDC45. J. Biol. Chemistry 1998; 273, 18205-18209.

  24. Renshaw A A, Loughlin K R, Dutta A. Cyclin A and Mib1 (Ki67) as markers of proliferation in primary renal neoplasms. Modern Pathology. 1998; 10, 963-966.

  25. Quintana DG, Thome KC, Hou ZH, Ligon AH, Morton C C and Dutta A. ORC5L, a new member of the human Origin Recognition Complex, is deleted in uterine leiomyomas and malignant myeloid diseases. J. Biol. Chemistry 1998; 273, 27137-27145.

  26. Qiu X B, Lin Y L, Thome K C, Pian P, Schlegel B P, Weremowicz S, Parvin J D, Dutta A. An Eukaryotic RuvB-like Protein (RUVBL1) Essential for Growth. J. Biol. Chemistry 1998; 273, 27786-27793.

  27. Quade B J, Park J J, Crum C P, Sun D, Dutta A. In vivo cyclin E expression as a marker for early cervical neoplasia. Modern Pathology. 1998; 11, 1238-1246.

  28. Pinto S, Quintana D G, Smith P, Mihalik R M, Hou Z -H, Boynton S, Jones C J, Hendricks M, Velinzon K, Wohlschlegel J A, Austin R J, Lane W S, Tully T* and Dutta A*. latheo encodes a subunit of the Origin Recognition Complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Neuron. 1999; 23, 45-54. * Co-corresponding authors.

  29. Datta M W, Renshaw A A, Dutta A, Hoffman M A and Loughlin KR. Evaluation of cyclin expression in testicular germ cell tumors: cyclin E correlates with tumor type, advanced clinical stage, and pulmonary metastasis. Modern Pathology. 2000; 13, 667-672

  30. Dhar S K and Dutta A. Identification of the human ORC6 homolog. J. Biol. Chemistry. 2000; 275, 34983-34988..

  31. Thome K C, Dhar S K, Quintana D G, Delmolino L, Shahsafaei A and Dutta A. Subsets of human ORC subunits are expressed in non-proliferating cells and associate with non-ORC proteins. J. Biol. Chemistry. 2000; 275, 35233-35241.

  32. Yamaguchi R and Dutta A. Proteasome inhibitors alter the orderly progression of DNA synthesis in S phase of HeLa cells and lead to re-replication of DNA. Exptl. Cell Research. 2000; 261, 271-283.

  33. Wohlschlegel J A, Dwyer B, Dhar S K, Cvetic C, Walter J and Dutta A. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science. 2000; 290, 2309-2312. (Accompanied by Perspectives essay in Science)

  34. Takeda D, Wohlschlegel J A, and Dutta A. A bipartite substrate recognition motif for cyclin-dependent kinases. J. Biol. Chemistry. 2001; 276, 1993-1997.

  35. Jonsson Z O, Dhar S K, Narlikar G, Auty R, Wagle N, Pellman D, Pratt R E, Kingston R and Dutta A. Rvb1p and Rvb2p are essential components of a chromatin remodeling complex that regulates transcription of over 5% of yeast genes. J. Biol. Chemistry. 2001; 276,16279-16288.

  36. Yoshida K, Kuo F, George E L, Sharpe A H and Dutta A. Requirement of CDC45 for postimplantation mouse development. Mol. Cell. Biol. 2001; 21, 4598-4603.

  37. Wohlschlegel J A, Dwyer B, Takeda D and Dutta A. A mutational analysis of the Cy motif from p21 reveals sequence degeneracy and specificity for different cyclin-dependent kinases. Mol. Cell. Biol. 2001; 21, 4868-4874.

  38. Delmolino L M, Saha P and Dutta A. Multiple mechanisms regulate subcellular localization of human CDC6: NLS, NES and phosphorylation. J.Biol. Chemistry. 2001; 276, 26947-26954.

  39. Dhar S K, Delmolino L M and Dutta A. Architecture of the human Origin Recognition Complex. J Biol. Chemistry, 2001; 276, 29067-29071.

  40. Dhar S K, Yoshida K, Machida Y, Khaira P, Chaudhuri B, Wohlschlegel J A, Leffak M, Yates J and Dutta A. Replication from oriP of Epstein-Barr Virus requires human ORC and is inhibited by geminin. Cell, 2001; 106, 287-296.

  41. Chaudhuri B, Xu H, Todorov I, Dutta A and Yates J L. Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus. . Proc Natl Acad Sci U S A. 2001; 98, 10085-10089.

  42. Wohlschlegel J A, Dhar SK, Prokhorova TA, Dutta A* and Walter J*. Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates binding of Cdc45. Molecular Cell. 2002; 9, 233-240. * Co-corresponding authors. (F1000)

  43. Wohlschlegel J A, Kutok J L , Weng A P and Dutta A. Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am. J. Pathology 2002; 161, 267-273.

  44. Ukomadu C and Dutta A. Inhibition of cdk2 activating phosphorylation by mevastatin. J. Biol. Chemistry 2003; 278, 4840-4846.

  45. Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, Wagle N, Hwang D S and Dutta A. A p53 dependent checkpoint pathway prevents re-replication. Molecular Cell 2003; 11, 997-1008. (Cover Image)

  46. Ukomadu C and Dutta A. p21 dependent inhibition of colon cancer cell growth by mevastatin is independent of inhibition of G1 cyclin-dependent kinases. J. Biol. Chem. 2003; 278, 43586

  47. Saxena S, Jonsson Z O and Dutta A. Small RNAs with imperfect match to endogenous mRNA repress translation: implications for off-target activity of siRNA in mammalian cells. J. Biol. Chem. 2003; 278, 44312-44319.

  48. Yoshida K, Oyaizu N, Dutta A and Inoue I. The destruction box of human Geminin is critical for proliferation and tumor growth in human colon cancer cells. Oncogene. 2004; 23, 58-70.

  49. Zhu W, Chen Y and Dutta A. Re-replication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol. Cell. Biol. 2004; 24, 7140-7150. (Cover Image)

  50. Saxena S, Yuan P, Dhar SK, Senga T, Takeda D, Robinson H, Kornbluth SA, Swaminathan K and Dutta A. A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. Molecular Cell, 2004; 15, 245-258.

  51. Jonsson Z O, Jha S, Wohlschlegel J A and Dutta A. Rvb1p/Rvb2p recruit Arp5p and assemble a functional Ino80 chromatin remodeling complex. Molecular Cell, 2004; 16, 465-477.

  52. ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science, 2004;306, 636-640.

  53. Lee YS, Kim HK, Chung S, Kim KS, and Dutta A. Depletion of human microRNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation. J Biol Chem. 2005; 280, 16635-16641.

  54. Jeon Y, Bekiranov S, Karnani N, Kapranov P, Ghosh S, MacAlpine D, Lee C, Hwang DS, Gingeras T and Dutta A. Temporal profile of replication of human chromosomes. Proc. Natl. Acad. Sci. USA. 2005; 102, 6419-6424.

  55. Takeda D Y, Parvin J D and Dutta A. Degradation of Cdt1 during S phase is SKP2 independent and is required for efficient progression of mammalian cells through S phase. J. Biol. Chem. 2005; 280, 23416-23423.

  56. Machida Y J, Teer J K and Dutta A. Acute reduction of an ORC subunit in human cells reveals a requirement of ORC for CDK2 activation. J. Biol. Chem. 2005; 280, 27624-27630.

  57. Takeda D Y, Shibata Y, Parvin J D and Dutta A. Recruitment of ORC or CDC6 is sufficient to create an artificial origin of replication in mammalian cells. Genes & Development. 2005; 19, 2827-36. (Research Highlight in Nature Reviews Genetics and Nature Reviews MCB; F1000) PMC1315390

  58. Senga T, Sivaprasad U, Zhu W, Park J H, Arias E E, Walter J C and Dutta A. PCNA is a co-factor for Cdt1 degradation by CUL4/DDB1 mediated N-terminal ubiquitination. J. Biol. Chem. 2006; 281, 6246-52. (F1000)

  59. Teer J K, Machida Y J, Labit H, Novac O, Hyrien O, Marheineke K, Zannis-Hadjopoulos M and Dutta A. Proliferating human cells hypomorphic for Orc2 and pre-RC formation have a defect in p53 activation and CDK2 kinase activation. J. Biol. Chem. 2006; 281, 6253-60.

  60. Ernkvist M, Aase K, Ukomadu C, Wohlschlegel J, Blackman R, Veitonmaki N, Bratt A, Dutta A and Holmgren L p130-Angiomotin associates with actin and controls endothelial cell shape. FEBS Journal, 2006; 273, 2000-11

  61. Zhu W and Dutta A. An ATR, BRCA1 mediated Fanconi Anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon re-replication. Mol. Cell. Biol. 2006; 26, 4601-11.

  62. Kim HK, Lee YS, Sivaprasad U, Malhotra A and Dutta A. Muscle-specific microRNA miR-206 promotes muscle differentiation. J. Cell Biol. 2006; 174, 677-687. (Cover Image and News Highlight in JCB; Research Highlight in Nature, 2006: 443, 4-5; F1000) PMC2064311

  63. Machida Y J, Machida Y, Chen Y, Gurtan A, Kupfer G M, D¿Andrea A D and Dutta A. UBE2T is the E2 in the Fanconi Anemia Pathway and Undergoes Negative Autoregulation. Molecular Cell, 2006; 23, 589-96.

  64. Sivaprasad U, Abbas T and Dutta A. Differential efficacy of HMG CoA reductase inhibitors on the cell cycle of prostate cancer cells. Molecular Cancer Therapeutics, 2006; 5: 2310-6.

  65. Machida Y J, Chen Y, Machida Y, Malhotra A, Sarkar S and Dutta A. Targeted Comparative RNAi (TARCOR) Analysis Reveals Differential Requirement of Genes Essential for Cell Proliferation. Mol. Biol. Cell. 2006; 17: 4837¿4845.

  66. Karnani N, Taylor C M, Malhotra A and Dutta A. Pan-S replication patterns and chromosomal domains defined by genome tiling arrays of ENCODE genomic areas. Genome Research, 2007; 17 : 865-76. (F1000 citation)

  67. Machida YJ and Dutta A. The APC/C Inhibitor, Emi1, Is Essential for Prevention of Rereplication. Genes & Development, 2007; 21:184-194. (F1000 citation) PMC1770901

  68. Abbas T, Jha S, Sherman NE and Dutta A. Autocatalytic Phosphorylation of CDK2 at the Activating Thr160. Cell Cycle, 2007; 6:843-52. (F1000 citation)

  69. Lee YS and Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes & Development, 2007; 21:1025-30. (Accompanied by a Perspectives essay). PMC1855228

  70. ENCODE project consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project consortium. Nature, 2007; 447: 799-816. (Our group provided and analyzed the DNA replication data for the consortium; F1000 citation.) PMC2212820

  71. Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, Nutt LK, Kornbluth S and Dutta A. Mcm10 and And-1/CTF4 recruit DNA polymerase ¿ to chromatin for initiation of DNA replication. . Genes & Development, 2007; 21:2288-99. (F1000 citation)

  72. Lin JJ and Dutta A. ATR pathway is the primary pathway for activating G2/M checkpoint induction after re-replication. J. Biol. Chem. 2007; 282:30357-62 (Highlighted as ¿Research Highlight¿ in Nature Structural and Molecular Biology, 14:1061)

  73. Alpi A, Langevin F, Mosedale G, Machida YJ, Dutta A and Patel KJ. UBE2T, the FA core complex and FANCD2 are recruited independently to chromatin: A basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 2007; 27:8421-30

  74. Deng Z, Dheekollu J, Broccoli D, Dutta A and Lieberman PM. The Origin Recognition Complex Localizes to Telomere Repeats and Prevents Telomere-Circle Formation. Current Biology. 2007; 17:1989-95.

  75. Teer JK and Dutta A. Human Cdt1 lacking the evolutionarily conserved region that interacts with MCM2-7 is capable of inducing re-replication. J. Biol. Chem. 2008; 283:6817-25.

  76. Jha S, Shibata E and Dutta A. Human Rvb1/Tip49 is required for the HAT activity of TIP60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage. Mol. Cell. Biol. 2008; 28:2690-700.

  77. Lew DJ, Burke DJ and Dutta A. The immortal strand hypothesis: How could it work? Cell, 2008; 133:21-23.

  78. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M and Dutta A. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4-cdt2 ubiquitin ligase complex. Genes & Development, 2008; 22:2496-506. PMC2546691

  79. Torreira E, Jha S, López-Blanco JR, Arias-Palomo E, Chacón P, Cañas C, Ayora S, Dutta A and Llorca O. Architecture of the pontin/reptin complex, essential in the assembly of several macromolecular complexes. Structure, 2008: 16:1511-20. PMC2577609

  80. Shibata Y, Malhotra A, Bekiranov S and Dutta A. Yeast genome analysis identifies chromosomal translocation, gene conversion events and several sites of Ty element insertion. Nucleic Acids Research, 2009: 37:6454-65. PMC2770650

  81. Lee YS, Shibata Y, Malhotra A and Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs).  Genes & Development, 2009; 23:2639-49. PMC2779758

  82. Machida YJ, Machida Y, Vashisht A, Wohlschlegel JA and Dutta A. The Deubiquitinating Enzyme BAP1 Regulates Cell Growth via Interaction with HCF-1. J. Biol. Chem., 2009; 284:34179-88. PMC2797188

  83. Terai K, Abbas T, Jazaeri AA and Dutta A. CRL4Cdt2 E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis.  Molecular Cell, 2010; 37:143-149. PMC2818832

  84. Karnani N, Taylor CM, Malhotra A and Dutta A. Genomic study of replication initiation in human chromosomes reveals the influence of transcription regulation and chromatin structure on origin selection. Mol. Biol. Cell. 2010; 21:393-404 PMC2814785

  85. Jazaeri AA, Ferriss JS, Bryant JL, Dalton MS, Dutta A. Evaluation of EVI1 and EVI1s (Delta324) as potential therapeutic targets in ovarian cancer. Gynecol Oncol. 2010, 118:189-95

  86. Sarkar S, Dey BK and Dutta A. MiR-322/424 and 503 are induced during muscle differentiation and promote cell-cycle quiescence and differentiation by downregulation of Cdc25A. Mol. Biol. Cell. 2010, 21:2138-49

  87. Jha S, Vande Pol S, Banerjee NS, Dutta AB, Chow LT, and Dutta A. Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60 dependent transcriptional regulation and apoptotic pathway. Molecular Cell, 2010, 38:700-11 (F1000 citation) PMC2886028

  88. Shibata Y, Malhotra A and Dutta A. Detection of DNA fusion junctions for BCR-ABL translocations by Anchored ChromPET. Genome Med. 2010, 2:70. PMID: 20860819 (Highly Accessed)

  89. Abbas T, Shibata E, Park J, Jha S, Karnani N and Dutta A. CRL4Cdt2 Regulates Cell Proliferation and Histone Gene Expression by Targeting PR-Set7/Set8 for Degradation. Molecular Cell, 2010, 40: 9-21. (Featured Article) PMC2966975

  90. Lin JJ, Milhollen MA, Smith PG, Narayanan U and Dutta A. Transient Exposure of HCT116 to MLN4924 Induces Re-replication by Stabilizing Cdt1 in S Phase, Leading to Checkpoint Activation, Apoptosis and Cellular Senescence. Cancer Research, Cancer Res. 2010 Dec 15;70(24):10310-20.
  91. Dey BK, Gagan J and Dutta A. MiR-206 and -486 induce myoblast differentiation by downregulating Pax7. Mol Cell Biol. 2011 Jan;31(1):203-14.

  92. Mesner LD, Valsakumar V, Karnani N, Dutta A, Hamlin JL, Bekiranov S. Bubble-chip analysis of human origin distributions demonstrates on a genomic scale significant clustering into zones and significant association with transcription. Genome Res. 2011 Mar;21(3):377-89. Epub 2010 Dec 20.

  93. Sun D, Lee YS, Malhotra A, Kim HK, Matecic M, Evans C, Jensen RV, Moskaluk CA, Dutta A. miR-99 family of MicroRNAs suppresses the expression of prostate-specific antigen and prostate cancer cell proliferation. Cancer Res. 2011 Feb 15;71(4):1313-24. Epub 2011 Jan 6.

  94. Karnani N, Dutta A. The effect of the intra-S-phase checkpoint on origins of replication in human cells. Genes Dev. 2011 Mar 15;25(6):621-33.

  95. Keaton M and Dutta A. Nuclear Scaffold Attachment Sites within ENCODE Regions Associate with Actively Transcribed Genes, PLOS One, 2011; 6 : e17912. PMC3056778

  96. Gagan JR, Dey BK, Layer R, Yan Z and Dutta A. MICRORNA-378 targets the myogenic repressor MyoR during myoblast differentiation, J. Biol. Chem., 2011; 286:19431-8. PMC3103322

  97. Shibata E, Abbas T, Huang X, Wohlschlegel JA and Dutta A. Selective ubiquitylation of p21 and Cdt1 by UbcH8 and Ube2G ubiquitin-conjugating enzymes via the CRL4-Cdt2 ubiquitin ligase complex. Mol. Cell Biol., 2011; 31:3136-45 PMC3147600

  98. Van Rechem C, Black JC, Abbas TA, Allen A, Rinehart CA, Yuan GC, Dutta A, Whetstine JR. The SKP1 - Cul1 - F-box and Leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A). J Biol Chem. 2011; 286:30462-70. PMC3162406

  99. Jazaeri AA, Bryant JL, Park H, Li H, Dahiya N, Stoler MH, Ferriss JS, Dutta A. Molecular requirements for transformation of fallopian tube epithelial cells into serous carcinoma. Neoplasia. 2011 13:899-911. PMC3201567

  100. Shibata Y, Kumar P, Layer R, Willcox S, Gagan JR, Griffith JD, Dutta A. Extrachromosomal MicroDNAs and Chromosomal Microdeletions in Normal Tissues. Science. 2012; 336:82-6 F1000 citation. PMID: 22403181

  101. Mueller AC, Sun D, Dutta A. The miR-99 family regulates the DNA damage response through its target SNF2H. Oncogene. 2012; Apr 23. doi: 10.1038/onc.2012.131. [Epub ahead of print]. PMC3407337

  102. Dey BK, Gagan JR, Yan Z, Dutta A. MiR-26a is required for skeletal muscle differentiation and regeneration in mice. Genes & Development. 2012; 26:2180-2191. PMC3465739

  103. Gagan JR, Dey BK, Layer R, Yan Z and Dutta A. Notch3 and Mef2c Are Mutually Antagonistic via Mkp1 and miR-1/206 in Differentiating Myoblasts. J. Biol. Chem. 2012; 287:40360-70. PMC3504751

  104. Gupta A, Jha S, Engel DA, Ornelles DA and Dutta A. Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator E1A. Oncogene. In press. 2013. 2012 Nov 26. doi: 10.1038/onc.2012.534. [Epub ahead of print]

  105. Jha S, Gupta A, Dar A and Dutta A. RVBs are required for assembling a functional TIP60 complex. Mol Cell Biol. 2013, 33:1164-74. PMC3592018

  106. Sun D, Layer R, Mueller AC, Cichewicz M, Negishi M, Paschal BM and Dutta A. Regulation of several androgen-induced genes through the repression miR 99a/let-7c/miR 125-b-2 miRNA cluster in prostate cancer cells. Oncogene. 2013. In press.

  107. Abbas T, Mueller AC, Shibata E, Keaton M, Rossi M and Dutta A.CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. Molecular Cell. 2013. 49:1147-58. PMC3615078

  108. Park J, Long DT, Lee KY, Abbas T, Shibata E, Negishi M, Luo Y, Schimenti JC, Gambus A, Walter JC, and Dutta A. The MCM8-9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination. Mol Cell Biol. 2013; 33:1632-44. PMC3624244

B. Reviews, Chapters and editorials

  1. Dutta A, Din S U , Brill S J, Stillman B. Phosphorylation of Replication Protein A: a role for cdc2 kinase in G1-S regulation. in The Cell Cycle, Cold Spring Harbor Symposium of Quantitative Biology. 1991; 56, 315-324.

  2. Stillman B, Bell S P, Dutta A, and Marahrens Y. Studies on DNA replication and the cell cycle. in Regulation of the eukaryotic cell cycle, CIBA Foundation, Symposium 170, Wiley Publishers, Chichester. 1992; 147-160.

  3. Dutta A. Trans-plication factors. Current Biology. 1993; 3, 709-712.

  4. Dutta A and Winchester E. SV40 based in vitro DNA replication assay. in "Cell Cycle: Materials and Methods", ed. Michelle Pagano. Springer-Verlag. Heidelberg. 1995; 175-185.

  5. Dutta A and Bell S P. Initiation of DNA replication in eukaryotic cells. Annual Review of Cell and Developmental Biology. 1997; 13, 293-332.

  6. Dutta A. Regulation of S phase. in "Cell Cycle Control", ed. Michelle Pagano. Springer-Verlag. Heidelberg. 1998; 35-56.

  7. Lin, Y-L and Dutta A. In vitro DNA replication. in ¿Current Protocols in Cell Biology¿, ed. Mary Dasso. John Wiley and Sons. New York. 1998; Chapter 11, Unit 11.5.

  8. Dutta A. Origin Recognition Complex and other eukaryotic initiator proteins. in ¿Experimental Medicine¿ special issue on DNA replication, ed. Takuya Ohashi and Akio Matsukage. Yodosha Co. Ltd. Tokyo. 1998; 16, 53-60.

  9. Quintana D.G. and Dutta A. The metazoan origin recognition complex. Frontiers in Biosciences. 1999; 4, 805-815.

  10. Bell S P. and Dutta A. Initiation of DNA replication in eukaryotic cells. Annual Review of Biochemistry. 2002; 71, 333-374.

  11. Wohlschlegel J A, Dutta A and Dhar S K. ORC and the initiation of DNA replication. In Eukaryotic DNA Replication for ChemTracts - Biochemistry & Molecular Biology; ed M. L. Depamphilis. 2002; 15, 533-543.

  12. Saxena S. and Dutta A. Geminin-Cdt1 balance is critical for genetic stability. In Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis- Stress Response; ed Nic Denko and Al Fornace, 2005; 569, 111-121.

  13. Machida Y J and Dutta A. Cellular checkpoint mechanisms monitoring proper initiation of DNA replication. J. Biological Chemistry, 2005; 280, 6253-6256.

  14. Blow J A and Dutta A. Preventing re-replication of chromosomal DNA. Nature Reviews Molecular Cell Biology, 2005; 6, 476-486.

  15. Takeda D and Dutta A. DNA replication and progression through S phase. Oncogene, 2005; 24, 2827-2843.

  16. Zhu W, Abbas T and Dutta A. DNA replication and genomic instability. "Genome instability and cancer development", ed. Erich Nigg, Series: Advances in Experimental Medicine and Biology, 2005; 570, 249-279 .

  17. Karnani N, Dutta A. Nuclear localization of RFC40 by RIalpha: a link between cellular signaling and proliferation. Cancer Biol Ther. 2005; 4, 438-9.

  18. Teer, J.K. and Dutta, A. (2006) Regulation of S Phase. In: Kaldis, P. (ed.) Cell Cycle Regulation. Results and Problems in Cell Differentiation, vol. 42. Springer Berlin, Heidelberg, New York, pp 31-64.

  19. Machida YJ, Hamlin JL and Dutta A. Right place, right time, and only once: replication initiation in metazoans. Cell. 2005; 123, 13-24.

  20. Sivaprasad U, Dutta A and Bell SP. Assembly of Pre-replication Complexes. In DNA replication and human disease (ed. M.L. DePamphilis). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. 2006; pp. 63-88.

  21. Abbas T and Dutta A. CDK2-Activating Kinase (CAK): More Questions than Answers. Cell Cycle. 2006; 5, 1123-1124.

  22. Lee YS and Dutta A. MicroRNAs: small but potent oncogenes or tumor suppressors. Curr. Opinion in Investigational Drugs 2006; 7, 560-564.

  23. Zhu W and Dutta A. Activation of fanconi anemia pathway in cells with re-replicated DNA. Cell Cycle. 2006; 5, 2306-2309

  24. Dutta A. Chaotic license for genetic instability and cancer. Nature Genetics, 2007; 39, 10-11.

  25. Sivaprasad U, Machida YJ and Dutta A. APC/C - the master controller of origin licensing? Cell Division, 2007; 2, 8.

  26. Hook S, Lin JJ and Dutta A. Mechanisms to Control Rereplication and Implications for Cancer. Curr. Opinion Cell Biol. 2007; 19:663-71. PMC2174913

  27. Karnani N, Taylor CM and Dutta A. Microarray analysis of DNA replication timing. In Microarray Analysis of the Physical Genome (ed. J.R. Pollack), Methods in Molecular Biology. Humana Press. Springer Science. Totowa, New Jersey. 2009: 191-203.

  28. Lee YS and Dutta A. MicroRNAs in cancer. Ann. Review of Pathology. 2009; 4:199-227 PMC2769253

  29. Abbas T and Dutta A. p21 in cancer: intricate networks and multiple activities. Nature Reviews Cancer. 2009; 9:400-414. PMC2722839

  30. Jha S and Dutta A. RVB1/RVB2: running rings around molecular biology. Molecular Cell. 2009; 34:521-33. PMC2733251

  31. Karnani N, Taylor CM, Dutta A. Microarray analysis of DNA replication timing. Methods Mol Biol. 2009;556:191-203.

  32. Abbas T, Dutta A. CRL4Cdt2: Master coordinator of cell cycle progression and genome stability. Cell Cycle. 2011; 10, Issue 2, 241-249

  33. Keaton M and Dutta A. Rad18 emerges as a critical regulator of the Fanconi Anemia pathway. Cell Cycle 2011; 10: in press.

  34. Mueller AC, Keaton M and Dutta A. DNA replication in the mirror: Mammalian Treslin-TopBP1 interaction reflects yeast Sld3-Dpb11. Current Biology 2011; 21:R638-40.

  35. Zhang Y, Dutta A, Abounader R. The role of microRNAs in glioma initiation and progression. Front Biosci. 2012;17:700-12

  36. Gagan J, Dey BK, Dutta A. MicroRNAs regulate and provide robustness to the myogenic transcriptional network. Curr Opin Pharmacol. 2012; 12:383-8 PMC3369106

  37. Dey BK, Mueller AC, Dutta A. Non-micro-short RNAs: the new kids on the block. Mol Biol Cell. 2012; 23:4664-7. PMC3521675

  38. Abbas T, Keaton MA and Dutta A. Genomic Instability and Cancer. In DNA replication and human disease (ed. M.L. DePamphilis). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. In press.

  39. Rosenbaum J., Baek SH, Dutta A, Houry WA, Huber O, Hupp TR and Matias PM. The emergence of the conserved AAA+ ATPases Pontin and Reptin on the signaling landscape. Science Signaling, 2013; 6:mr1. doi: 10.1126/scisignal.2003906.

C.  Patents
 

  1. Tully, T., Dutta A. and Broadie K. WO/2000/060078. Latheo encoded a subunit of the origin of recognition complex.

  2. Dhar S.K and Dutta A. U.S. Patent no., 6,890,743. Geminin and Orc3N inhibit replication of herpesviruses, papillomaviruses and polyomaviruses.

  3. Dutta A, Malhotra A and Shibata Y. U.S. Provisional Patent 61/099,943. Anchored Chrompets for Identifying Chromosomal Translocations in Disease.

 


Links

The slides for class "MICR811" can be found here

Some photos from "Lab Barbecue 2010" can be found here


Contact Address

Department of Biochemistry and Molecular Genetics,

Room no. 1232, Jordan Hall,

University of Virginia,

Charlottesville, VA 22908

Ph: 434 - 924 - 2466


Please forward all comments and questions to pk7z@virginia.edu
12/14/2010