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The sticky business of histone H2AX in V(D)J recombination, maintenance of genomic stability, and suppression of lymphoma

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Abstract

DNA double strand breaks (DSBs) induced during cellular metabolism, DNA replication, and genomic rearrangement events lead to phosphorylation of the H2AX core histone variant in surrounding chromatin. H2AX is essential for normal DSB repair, maintenance of genomic stability, and suppression of lymphomas with clonal translocations and intra-chromosomal deletions. One current focus of our lab is to elucidate mechanisms through which H2AX functions in the cellular DNA damage response using V(D)J recombination as a model system. A number of potential H2AX functions can be readily tested using novel experimental approaches developed in our lab. These putative functions include: (1) modulation of chromatin accessibility to facilitate kinetics of DSB repair, (2) stabilization of broken DNA strands to maintain ends in close proximity, and (3) amplification of DNA damage signals. Here, we summarize our recent efforts in elucidating mechanisms by which H2AX functions during V(D)J recombination to coordinate DSB repair with cellular proliferation and survival to prevent translocations and suppress lymphomagenesis.

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Acknowledgments

C.H.B. is a Pew Scholar in the Biomedical Sciences. This work was supported by the Department of Pathology and Center for Childhood Cancer Research of the Children’s Hospital of Philadelphia (C.H.B.), the Abramson Family Cancer Research Institute (C.H.B.), and the National Cancer Institute Grant CA125195 (C.H.B.).

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  1. Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Bu Yin

  2. Cancer Biology Program, Cell and Molecular Biology Graduate Group, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 807A Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA, 19104-4318, USA

    Bu Yin & Craig H. Bassing

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Yin, B., Bassing, C.H. The sticky business of histone H2AX in V(D)J recombination, maintenance of genomic stability, and suppression of lymphoma. Immunol Res 42, 29–40 (2008). https://doi.org/10.1007/s12026-008-8030-4

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