TY - JOUR
T1 - Role of non-homologous end joining in V(D)J recombination
AU - Malu, Shruti
AU - Malshetty, Vidyasagar
AU - Francis, Dailia
AU - Cortes, Patricia
N1 - Funding Information:
Acknowledgments We thank current and past members of the Cortes laboratory for their contribution to our work and Dr. Juan Carcamo, Mary Hanna, and Jennifer Chu for constructive suggestions and critical reading of the manuscript. A special thanks to Shreya Malu for performing the graphic design of the V(D)J recombination pathway. Work in the P.C. laboratory is supported in part by RO1 AI080755, RO1 AI070532, and R01 AI070880 from National Institute of health (NIH), and past support from the Irma T. Hirsch/Mo-nique Weill-Caullier Research Award, project R56AI070532-01A1 (NIH), RSG-04-191-01 LIB from the American Cancer Society, a Leukemia and Lymphoma Society Scholar Award and Program Project grant P01 AI061093 (NIH).
PY - 2012/12
Y1 - 2012/12
N2 - The pathway of V(D)J recombination was discovered almost three decades ago. Yet it continues to baffle scientists because of its inherent complexity and the multiple layers of regulation that are required to efficiently generate a diverse repertoire of T and B cells. The non-homologous end-joining (NHEJ) DNA repair pathway is an integral part of the V(D)J reaction, and its numerous players perform critical functions in generating this vast diversity, while ensuring genomic stability. In this review, we summarize the efforts of a number of laboratories including ours in providing the mechanisms of V(D)J regulation with a focus on the NHEJ pathway. This involves discovering new players, unraveling unknown roles for known components, and understanding how deregulation of these pathways contributes to generation of primary immunodeficiencies. A long-standing interest of our laboratory has been to elucidate various mechanisms that control RAG activity. Our recent work has focused on understanding the multiple protein-protein interactions and protein-DNA interactions during V(D)J recombination, which allow efficient and regulated generation of the antigen receptors. Exploring how deregulation of this process contributes to immunodeficiencies also continues to be an important area of research for our group.
AB - The pathway of V(D)J recombination was discovered almost three decades ago. Yet it continues to baffle scientists because of its inherent complexity and the multiple layers of regulation that are required to efficiently generate a diverse repertoire of T and B cells. The non-homologous end-joining (NHEJ) DNA repair pathway is an integral part of the V(D)J reaction, and its numerous players perform critical functions in generating this vast diversity, while ensuring genomic stability. In this review, we summarize the efforts of a number of laboratories including ours in providing the mechanisms of V(D)J regulation with a focus on the NHEJ pathway. This involves discovering new players, unraveling unknown roles for known components, and understanding how deregulation of these pathways contributes to generation of primary immunodeficiencies. A long-standing interest of our laboratory has been to elucidate various mechanisms that control RAG activity. Our recent work has focused on understanding the multiple protein-protein interactions and protein-DNA interactions during V(D)J recombination, which allow efficient and regulated generation of the antigen receptors. Exploring how deregulation of this process contributes to immunodeficiencies also continues to be an important area of research for our group.
KW - Genomic stability
KW - Immunodeficiencies
KW - Non-homologous end joining (NHEJ)
KW - V(D)J recombination
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U2 - 10.1007/s12026-012-8329-z
DO - 10.1007/s12026-012-8329-z
M3 - Review article
C2 - 22569912
AN - SCOPUS:84867847788
SN - 0257-277X
VL - 54
SP - 233
EP - 246
JO - Immunologic Research
JF - Immunologic Research
IS - 1-3
ER -