Recognition of DNA damage activates a signalling cascade involving post-translational modifications that result in cell cycle arrest and DNA repair initiation. In response to DNA double-strand breaks, histone H2AX is quickly phosphorylated at Ser139 (pSer139) and is thought to be progressively dephosphorylated at Tyr142, resulting in a temporal switch from a diphosphorylated (pSer139 and pTyr142) to a monophosphorylated (pSer139) state. Here, the authors provide evidence that diphosphorylated H2AX (diγH2AX) exists in vivo in the early stages of DNA damage repair, and that the DNA damage response protein microcephalin (MCPH1) directly interacts with both diγH2AX and γH2AX. The authors speculate that MCPH1 is recruited to sites of damage as an early response to DNA double-strand breaks, and that progressive dephosphorylation of pTyr142 enhances the interaction between γH2AX and MCPH1, which could result in the recruitment of other repair factors.
ORIGINAL RESEARCH PAPER
Singh, N. et al. Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X by DNA damage response protein MCPH1. Proc. Natl Acad. Sci. USA 109, 14381–14386 (2012)
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Jones, B. Rapid response. Nat Rev Mol Cell Biol 13, 602 (2012). https://doi.org/10.1038/nrm3446
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DOI: https://doi.org/10.1038/nrm3446