Acetylation of BLM protein regulates its function in response to DNA damage

Acetylation of BLM protein regulates its function in response to DNA damage
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BLM 蛋白的乙酰化可调节其响应 DNA 损伤的功能

DOI:
10.1039/c7ra06666j
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发表时间:
2017
期刊:
影响因子:
3.9
通讯作者:
Luo Jianyuan
Luo Jianyuan
中科院分区:
化学3区
文献类型:
--
作者:
Wang Yankun;Luo Jianyuan

文献摘要

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布卢姆综合征是一种常染色体隐性遗传疾病,具有癌症易感性和由blm基因突变引起的过早衰老的表型。BLM属于RecQ DNA解旋酶家族,在维持基因组稳定性中起作用。在这项研究中,我们发现几个赖氨酸残基的BLM乙酰化细胞。CBP/p300和SIRT 1调控BLM的动态乙酰化水平。我们进一步确定了五个赖氨酸,K476,K863,K1010,K1329和K1411,是主要的乙酰化位点。用不同的DNA损伤剂处理细胞,发现BLM的乙酰化对依托泊苷和羟基脲的反应不同,这表明BLM的乙酰化可能在DNA修复中具有多种功能。
Bloom syndrome is an autosomal recessive disease with phenotypes of cancer predisposition and premature aging caused by mutations of the blm gene. BLM belongs to the RecQ DNA helicase family and functions in maintaining genomic stability. In this study, we found that several lysine residues of BLM were acetylated in cells. The dynamic acetylation levels of BLM were regulated by CBP/p300 and SIRT1. We further identified that five lysines, K476, K863, K1010, K1329, and K1411, are the major acetylation sites. Treating cells with different DNA damage agents found that acetylation of BLM was different in response to etoposide and hydroxyurea, suggesting that BLM acetylation may have multiple functions in DNA repair.