Histone H2A Ser122 facilitates DNA repair

Department of Biochemistry, University of Cambridge, UK.
Genetics (Impact Factor: 5.96). 07/2005; 170(2):543-53. DOI: 10.1534/genetics.104.038570
Source: PubMed


DNA repair takes place in the context of chromatin. Recently, it has become apparent that proteins that make up and modulate chromatin structure are involved in the detection and repair of DNA lesions. We previously demonstrated that Ser129 in the carboxyl-terminal tail of yeast histone H2A is important for double-strand-break responses. By undertaking a systematic site-directed mutagenesis approach, we identified another histone H2A serine residue (Ser122) that is important for survival in the presence of DNA-damaging agents. We show that mutation of this residue does not affect DNA damage-dependent Rad53 phosphorylation or G(2)/M checkpoint responses. Interestingly, we find that yeast lacking H2A S122 are defective in their ability to sporulate. Finally, we demonstrate that H2A S122 provides a function distinct from that of H2A S129. These data demonstrate a role for H2A S122 in facilitating survival in the presence of DNA damage and suggest a potential role in mediating homologous recombination. The distinct roles of H2A S122 and S129 in mediating these responses suggest that chromatin components can provide specialized functions for distinct DNA repair and survival mechanisms and point toward the possibility of a complex DNA damage responsive histone code.

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Available from: Jessica Downs, Oct 30, 2014
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    • "There are reports of other histone posphorylations in response to DNA damage independent of gamma-H2AX. For example, yeast H2A is phosphorylated at serine 122 upon DNA damage and this residue seems to be essential for cell survival in the presence of DNA damaging agents (Wyatt et al., 2003; Harvey et al., 2005). Histone methylation does not seem to be involved much in DNA repair. "
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    • "Spheroplasts were prepared as previously described (33,34). Briefly, yeast cells were synchronized in G2/M phase with nocodazole for 3 h at 23°C and cultured for 1 h at non-permissive temperature (37°C), and then 1 × 109 cells were harvested. "
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    • "In addition to serine 129 in the H2A C-terminal tail, H2A serine 122 was also recently shown to be involved in mediating cell survival after several types of DNA damage had occurred. Although serine 122 can be phosphorylated in vivo and is located in close proximity to S129, its function in repair is independent from that of S129 (Wyatt et al. 2003; Harvey et al. 2005; J.D. Moore, O. Yazgan, Y. Ataian, and J.E. Krebs, unpublished results). Taken together, it is clear that histone modifications play a complicated role in DSB repair. "
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