Interaction between RECQL4 and OGG1 promotes repair of oxidative base lesion 8-oxoG and is regulated by SIRT1 deacetylase
Interaction between RECQL4 and OGG1 promotes repair of oxidative base lesion 8-oxoG and is regulated by SIRT1 deacetylase
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DOI：
10.1093/nar/gkaa392
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发表时间：
2020-07-09
影响因子：
14.9
通讯作者：
Bohr, Vilhelm A.
中科院分区：
文献类型：
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作者：
Duan, Shunlei;Han, Xuerui;Bohr, Vilhelm A.
OGG 1启动的碱基切除修复（BER）是8-氧代鸟嘌呤（8-oxoG）氧化性DNA碱基损伤修复的主要途径。在这里，我们报告说，RECQL 4 DNA解旋酶，缺乏癌症倾向和过早老化的罗斯蒙-汤姆森综合征，物理和功能上与OGG 1相互作用。RECQL 4促进OGG 1的催化活性，RECQL 4缺陷导致缺陷的8-oxoG修复和增加的基因组8-oxoG。此外，我们表明，急性氧化应激导致增加RECQL 4乙酰化及其与OGG 1的相互作用。NAD（+）依赖性蛋白SIRT 1在体外和细胞中使RECQL 4脱乙酰化，从而控制DNA修复后OGG 1和RECQL 4之间的相互作用，并使RECQL 4保持在低乙酰化状态。总的来说，我们发现RECQL 4通过与OGG 1相互作用参与8-oxoG修复，SIRT 1通过控制RECQL 4-OGG 1相互作用间接调节8-oxoG的BER。
OGG1 initiated base excision repair (BER) is the major pathway for repair of oxidative DNA base damage 8-oxoguanine (8-oxoG). Here, we report that RECQL4 DNA helicase, deficient in the cancer-prone and premature aging Rothmund-Thomson syndrome, physically and functionally interacts with OGG1. RECQL4 promotes catalytic activity of OGG1 and RECQL4 deficiency results in defective 8-oxoG repair and increased genomic 8-oxoG. Furthermore, we show that acute oxidative stress leads to increased RECQL4 acetylation and its interaction with OGG1. The NAD(+)-dependent protein SIRT1 deacetylates RECQL4 in vitro and in cells thereby controlling the interaction between OGG1 and RECQL4 after DNA repair and maintaining RECQL4 in a low acetylated state. Collectively, we find that RECQL4 is involved in 8-oxoG repair through interaction with OGG1, and that SIRT1 indirectly modulates BER of 8-oxoG by controlling RECQL4-OGG1 interaction.