title: The sticky business of histone H2AX in V(D)J recombination, maintenance of genomic stability, and suppression of lymphoma.
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.
authors.affiliation: Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Bu
authors.initials: B
authors.lastname: Yin
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bassing
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D015321:Gene Rearrangement; D042822:Genomic Instability; D006657:Histones / Q000502:physiology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008223:Lymphoma / Q000473:pathology*
chemical_list: D006657:Histones; D007135:Immunoglobulin Variable Region; C468783:H2AX protein, human; C475961:gamma-H2AX protein, mouse