title: H2AX may function as an anchor to hold broken chromosomal DNA ends in close proximity.
abstract: The histone H2A variant, H2AX, is a core component of chromatin that is phosphorylated in chromatin flanking DNA double strand breaks (DSBs). Here, we summarize H2AX functions and outline a specific "anchoring" model, that can explain the translocation prone phenotype of H2AX-deficient and H2AX/p53-deficient mice. We also discuss how this model of H2AX function could account for some aspects of the genomic instability and cancer prone human phenotypes associated with Ataxia Telangiectasia (AT), Nijmegen Breakage Syndrome (NBS), Ataxia Telangiectasia Like Disorder (ATLD), and Bloom's Syndrome (BS).
authors.affiliation: The CBR Institute for Biomedical Research, The Children's Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bassing
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases