An H2A histone isotype, H2ac, associates with telomere and maintains telomere integrity

Chia Hsin Su, Ching Cheng, Tsai Yu Tzeng, I. Hsuan Lin, Ming Ta Hsu

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Telomeres are capped at the ends of eukaryotic chromosomes and are composed of TTAGGG repeats bound to the shelterin complex. Here we report that a replication-dependent histone H2A isotype, H2ac, was associated with telomeres in human cells and coimmunoprecipitates with telomere repeat factor 2 (TRF2) and protection of telomeres protein 1 (POT1), whereas other histone H2A isotypes and mutations of H2ac did not bind to telomeres or these two proteins. The amino terminal basic domain of TRF2 was necessary for the association with H2ac and for the recruitment of H2ac to telomeres. Depletion of H2ac led to loss of telomeric repeat sequences, the appearance of dysfunctional telomeres, and chromosomal instability, including chromosomal breaks and anaphase bridges, as well as accumulation of telomere-associated DNA damage factors in H2ac depleted cells. Additionally, knockdown of H2ac elicits an ATM-dependent DNA damage response at telomeres and depletion of XPF protects telomeres against H2ac-deficiency-induced G-strand overhangs loss and DNA damage response, and prevents chromosomal instability. These findings suggest that the H2A isotype, H2ac, plays an essential role in maintaining telomere functional integrity.
原文英語
文章編號e0156378
期刊PLoS One
11
發行號5
DOIs
出版狀態已發佈 - 五月 1 2016
對外發佈

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 農業與生物科學 (全部)

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