@article{f7f38facd39b46178e3fe1bc0510b75f,
title = "H2AX prevents DNA breaks from progressing to chromosome breaks and translocations",
abstract = "Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires activation-induced cytidine deaminase (AID) and involves joining of DSB intermediates by end joining. We find that AID-dependent IgH locus chromosome breaks occur at high frequency in primary H2AX-deficient B cells activated for CSR and that a substantial proportion of these breaks participate in chromosomal translocations. Moreover, activated B cells deficient for ATM, 53BP1, or MDC1, which interact with H2AX during the DSB response, show similarly increased IgH locus breaks and translocations. Thus, our findings implicate a general role for these factors in promoting end joining and thereby preventing DSBs from progressing into chromosomal breaks and translocations. As cellular p53 status does not markedly influence the frequency of such events, our results also have implications for how p53 and the DSB response machinery cooperate to suppress generation of lymphomas with oncogenic translocations.",
author = "Sonia Franco and Monica Gostissa and Shan Zha and Lombard, {David B.} and Murphy, {Michael M.} and Zarrin, {Ali A.} and Catherine Yan and Suprawee Tepsuporn and Morales, {Julio C.} and Adams, {Melissa M.} and Zhenkun Lou and Bassing, {Craig H.} and Manis, {John P.} and Junjie Chen and Carpenter, {Phillip B.} and Alt, {Frederick W.}",
note = "Funding Information: We thank Charles Lee, Hwei-Ling Cheng, Tiffany Borjeson, and Alyssa Riley for technical advice; Barbara Haskell for technical support; and all Alt lab members for helpful discussions. This work was supported by NIH Grants PO1CA092625-05 and 2PO1AI031541-15 (to F.W.A.), GM65812 (to P.B.C.), and RO1 CA89239 and CA92312 (to J.C.); a Long-Term Fellowship of the European Molecular Biology Organization (to S.F.); a Fellowship of the Leukemia and Lymphoma Society (to S.Z.); and a NIA/NIHKO8 Award (to D.B.L.). Z.L. is the recipient of a DOD Breast Cancer Postdoctoral Fellowship (DAMD17-03-1-0610). C.H.B. was a Lymphoma Research Foundation Fellow and is a Pew Scholar in the Biomedical Sciences. J.C. is a recipient of DOD Breast Cancer Career Development Award (DAMD17-02-1-0472). F.W.A. is a Howard Hughes Medical Institute investigator. ",
year = "2006",
month = jan,
day = "20",
doi = "10.1016/j.molcel.2006.01.005",
language = "English (US)",
volume = "21",
pages = "201--214",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}