Research Topics
Genomes and Genes | Dipanjan ChowdhurySummaryAffiliation: Harvard University Country: USA Publications
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Publications
A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replicationDipanjan Chowdhury
Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 31:33-46. 2008..Therefore, gamma-H2AX elimination at DNA damage foci is required for DNA damage repair, but accomplishing this task involves distinct phosphatases with potentially overlapping roles...- What goes on must come off: phosphatases gate-crash the DNA damage responseDong Hyun Lee
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Trends Biochem Sci 36:569-77. 2011..Here, we focus on serine/threonine phosphatases implicated in dephosphorylation of DNA repair factors, summarizing recent findings and speculating on untested roles of phosphatases in the DNA damage response... - Death by a thousand cuts: granzyme pathways of programmed cell deathDipanjan Chowdhury
Dana Farber Cancer Institute and Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts 02115, USA
Annu Rev Immunol 26:389-420. 2008..This review discusses what is known about granzyme-mediated pathways of cell death as well as recent studies that implicate granzymes in immune regulation and extracellular proteolytic functions in inflammation... - A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombinationDong Hyun Lee
1 Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA 2 Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts, USA
Nat Struct Mol Biol 17:365-72. 2010..These observations provide new insight into the role and regulation of RPA phosphorylation in HR-mediated repair... - miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cellsAshish Lal
Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
Nat Struct Mol Biol 16:492-8. 2009..Therefore, miR-24 upregulation in postreplicative cells reduces H2AX and makes them vulnerable to DNA damage... - gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repairDipanjan Chowdhury
CBR Institute for Biomedical Research and The Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 20:801-9. 2005..The effect of PP2A on gamma-H2AX levels is independent of ATM, ATR, or DNA-PK activity... - The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5'-diphosphate-ribose) polymerase-1Pengcheng Zhu
Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Blood 114:1205-16. 2009..Disrupting PARP-1, which is also a caspase target, is therefore required for efficient apoptosis by both caspase-independent and caspase-dependent pathways... - The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell deathDipanjan Chowdhury
CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 23:133-42. 2006..After granzyme A activates NM23-H1 to make single-stranded nicks, TREX1 removes nucleotides from the nicked 3' end to reduce the possibility of repair by rejoining the nicked ends... - A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recoveryMichael Christopher Keogh
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 439:497-501. 2006..The dephosphorylation of gammaH2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint... - miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elementsAshish Lal
Immune Disease Institute, Children s Hospital Boston, Department of Pediatrics, Harvard Medical School, MA 02115, USA
Mol Cell 35:610-25. 2009..The E2F2 3'UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by recognizing seedless but highly complementary sequences... - miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitorsPatryk Moskwa
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 41:210-20. 2011..Together these results suggest that miR-182-mediated downregulation of BRCA1 impedes DNA repair and may impact breast cancer therapy... - An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infectionDeborah Palliser
CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 439:89-94. 2006..These results suggest that siRNAs are attractive candidates for the active component of a microbicide designed to prevent viral infection or transmission... - Granzyme A, which causes single-stranded DNA damage, targets the double-strand break repair protein Ku70Pengcheng Zhu
The CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
EMBO Rep 7:431-7. 2006..Therefore, Ku70 has other antiapoptotic functions in GzmA-induced cell death, which are blocked when GzmA proteolyses Ku70... - DNA breaks and chromosome pulverization from errors in mitosisKaren Crasta
Department of Pediatric Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA
Nature 482:53-8. 2012..Pulverization of chromosomes in micronuclei may also be one explanation for 'chromothripsis' in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement... - RNAi and RNA-based regulation of immune system functionDipanjan Chowdhury
Center for Blood Research and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Adv Immunol 88:267-92. 2005..On the other hand, RNA editing and RNAi have an inverse relationship and RNA editing has an important role in viral immunity. These observations indicate unique roles for dsRNAs in the mammalian immune system... - Granzymes and cell deathDenis Martinvalet
Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
Methods Enzymol 442:213-30. 2008..This chapter discusses methods to study granzyme function in vitro under physiologically relevant experimental conditions... - RNA interference and cancer: endogenous pathways and therapeutic approachesDerek M Dykxhoorn
Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Adv Exp Med Biol 615:299-329. 2008..Possible strategies and obstacles to harnessing RNAi for cancer therapy will also be discussed... - Distinct passenger strand and mRNA cleavage activities of human Argonaute proteinsBingbing Wang
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA
Nat Struct Mol Biol 16:1259-66. 2009..We show that passenger strand cleavage and RNA chaperone activities that are intrinsic to both AGO1 and AGO2 are sufficient for RNA-induced silencing complex (RISC) loading... - Potential roles for short RNAs in lymphocytesDipanjan Chowdhury
Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
Immunol Cell Biol 83:201-10. 2005.... - Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptorsErwei Song
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Nat Biotechnol 23:709-17. 2005..Furthermore, an ErbB2 single-chain antibody fused with protamine delivered siRNAs specifically into ErbB2-expressing cancer cells. This study demonstrates the potential for systemic, cell-type specific, antibody-mediated siRNA delivery... - Mechanisms for feedback inhibition of the immunoglobulin heavy chain locusDipanjan Chowdhury
Centre for Blood Research, Boston, MA 02115, USA
Curr Opin Immunol 16:235-40. 2004..Similar transient signals may be responsible for enforcing allelic exclusion in other V(H) gene families. D-proximal V(H) genes, however, appear to be less susceptible to feedback inhibition... - Repeat organization and epigenetic regulation of the DH-Cmu domain of the immunoglobulin heavy-chain gene locusTirtha Chakraborty
Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD 21224, USA
Mol Cell 27:842-50. 2007..We propose that the intervening D(H) genes are actively suppressed by repeat-induced epigenetic silencing, which is reflected in their infrequent representation in DJ(H) junctions compared to the flanking D(H) genes... - Regulation of immunoglobulin heavy-chain gene rearrangementsDipanjan Chowdhury
Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD 21224, USA
Immunol Rev 200:182-96. 2004..VH genes are activated subsequently and, in part, by interleukin-7. These observations lead to a model for feedback inhibition of IgH rearrangements... - Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangementsDipanjan Chowdhury
Department of Biology, Brandeis University, Waltham, MA 02454, USA
Immunity 18:229-41. 2003..Thus, transient signals mediate V(H) gene activation and inactivation during development... - Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segmentsDavid G T Hesslein
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520 8011, USA
Genes Dev 17:37-42. 2003..The finding of transcribed, histone acetylated gene segments that fail to recombine suggests that a Pax5-dependent regulatory mechanism is required in addition to standard constraints of accessibility to control V(H) gene recombination...
Research Grants
- Investigate role of microRNA cluster 183-96-182 in DNA repair and radiosensitivitDipanjan Chowdhury; Fiscal Year: 2010..Identifying specific miRNAs that suppress DNA repair, and their functional impact upon the DNA repair pathways, and radiosensitivity of cells, will have significant clinical implications in cancer biology. ..