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Vipul Kumar
Howard Hughes Medical Institute
Non-homologous end joiningImmunoglobulin class switchingV(D)J recombinationLIG4DNA
8Publications
4H-index
123Citations
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Publications 8
Newest
#1S. Haihua ChuH-Index: 5
#2Jonathan ChabonH-Index: 1
Last. Putzer J. HungH-Index: 3
view all 17 authors...
Summary Repair of DNA double-stranded breaks (DSBs) during lymphocyte development is essential for V(D)J recombination and forms the basis of immunoglobulin variable region diversity. Understanding of this process in lymphogenesis has historically centered on the study of RAG1/2 recombinases and a set of classical non-homologous end-joining factors. Much less has been reported regarding the role of chromatin modifications on this process. Here, we show a role for the non-redundant histone H3 lys...
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#1Rohit A. Panchakshari (Harvard University)H-Index: 7
#2Xuefei Zhang (Harvard University)H-Index: 2
Last. Frederick W. Alt (Harvard University)H-Index: 157
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Ig heavy chain (IgH) class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double-strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region DSB ends by classical nonhomologous end-joining (C-NHEJ) and, in its absence, by alternative end-joining that is more biased to use longer junctional microhomologies (MHs). Deficiency for D...
15 CitationsSource
#1Hai Vu Nguyen (Harvard University)H-Index: 2
#2Junchao Dong (Harvard University)H-Index: 6
Last. Jean-Christophe BoriesH-Index: 5
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Abstract In B cells, Ig class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), the activity of which leads to DNA double-strand breaks (DSBs) within IgH switch (S) regions. Preferential targeting of AID-mediated DSBs to S sequences is critical for allowing diversification of antibody functions, while minimizing potential off-target oncogenic events. Here, we used gene targeted inactivation of histone methyltransferase (HMT) multiple myeloma SET domain (MMSE...
4 CitationsSource
#1Vipul KumarH-Index: 4
#2Frederick W. AltH-Index: 157
V(D)J recombination requires the formation and resolution of programmed DNA double-strand breaks (DSBs) to effect the gene rearrangements necessary for immunoglobulin and T cell receptor formation. Improper repair of DNA DSBs can lead to deleterious consequences for the cell, including loss of genetic information, cell death, and formation of chromosomal translocations. The classical nonhomologous end-joining (C-NHEJ) pathway is a major DNA DSB repair pathway that maintains cellular genomic inte...
1 CitationsSource
#1Vipul Kumar (HHMI: Howard Hughes Medical Institute)H-Index: 4
#2Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
Last. Valentyn Oksenych (HHMI: Howard Hughes Medical Institute)H-Index: 11
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Abstract Developing B and T lymphocytes generate programmed DNA double strand breaks (DSBs) during the V(D)J recombination process that assembles exons that encode the antigen-binding variable regions of antibodies. In addition, mature B lymphocytes generate programmed DSBs during the immunoglobulin heavy chain (IgH) class switch recombination (CSR) process that allows expression of different antibody heavy chain constant regions that provide different effector functions. During both V(D)J recom...
3 CitationsSource
#1Vipul Kumar (HHMI: Howard Hughes Medical Institute)H-Index: 4
#2Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
Last. Valentyn Oksenych (HHMI: Howard Hughes Medical Institute)H-Index: 11
view all 3 authors...
53BP1 a b s t r a c t Developing B and T lymphocytes generate programmed DNA double strand breaks (DSBs) during the V(D)J recombination process that assembles exons that encode the antigen-binding variable regions of antibodies. In addition, mature B lymphocytes generate programmed DSBs during the immunoglobulin heavy chain (IgH) class switch recombination (CSR) process that allows expression of different antibody heavy chain constant regions that provide different effector functions. During bot...
28 CitationsSource
#1Valentyn Oksenych (Harvard University)H-Index: 11
#2Vipul Kumar (Harvard University)H-Index: 4
Last. Frederick W. Alt (Harvard University)H-Index: 157
view all 7 authors...
Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB) repair pathway that is required for assembly of antigen receptor variable region gene segments by V(D)J recombination. Recombination activating gene endonuclease initiates V(D)J recombination by generating DSBs between two V(D)J coding gene segments and flanking recombination signal sequences (RS), with the two coding ends and two RS ends joined by C-NHEJ to form coding joins and signal joins, respect...
33 CitationsSource
The classical nonhomologous DNA end-joining (C-NHEJ) double-strand break (DSB) repair pathway in mammalian cells maintains genome stability and is required for V(D)J recombination and lymphocyte development. Mutations in the XLF C-NHEJ factor or ataxia telangiectasia-mutated (ATM) DSB response protein cause radiosensitivity and immunodeficiency in humans. Although potential roles for XLF in C-NHEJ are unknown, ATM activates a general DSB response by phosphorylating substrates, including histone ...
39 CitationsSource
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