Double-strand DNA breaks recruit the centromeric histone CENP-A

作者：Zeitlin Samantha G^*; Baker Norman M; Chapados Brian R; Soutoglou Evi; Wang Jean Y J; Berns Michael W; Cleveland Don W

来源：Proceedings of the National Academy of Sciences, 2009, 106(37): 15762-15767.

DOI：10.1073/pnas.0908233106

• chromatin
• DNA repair

The histone H3 variant CENP-A is required for epigenetic specification of centromere identity through a loading mechanism independent of DNA sequence. Using multiphoton absorption and DNA cleavage at unique sites by I-SceI endonuclease, we demonstrate that CENP-A is rapidly recruited to double-strand breaks in DNA, along with three components (CENP-N, CENP-T, and CENP-U) associated with CENP-A at centromeres. The centromere-targeting domain of CENP-A is both necessary and sufficient for recruitment to double-strand breaks. CENP-A accumulation at DNA breaks is enhanced by active non-homologous end-joining but does not require DNA-PKcs or Ligase IV, and is independent of H2AX. Thus, induction of a double-strand break is sufficient to recruit CENP-A in human and mouse cells. Finally, since cell survival after radiation-induced DNA damage correlates with CENP-A expression level, we propose that CENP-A may have a function in DNA repair.

• 出版日期2009-9-15