Distinct roles of XRCC1 in genome integrity in Xenopus egg extracts
Distinct roles of XRCC1 in genome integrity in Xenopus egg extracts
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DOI：
10.1042/bcj20190798
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发表时间：
2019-12-01
影响因子：
4.1
通讯作者：
Yan, Shan
中科院分区：
文献类型：
--
作者：
Cupello, Steven;Lin, Yunfeng;Yan, Shan
氧化性DNA损伤是最常见的DNA损伤之一。目前尚不清楚DNA修复和DNA损伤反应（DDR）途径在氧化应激后是如何协调和调节的。虽然XRCC1与DNA修复有关，但目前尚不清楚XRCC1如何修复和感知DNA氧化损伤。在这篇文章中，我们已经证明了XRCC1在爪蟾卵提取物氧化应激后的ATR-Chk1 DDR通路中是不可或缺的。虽然APE2对于SSB修复至关重要，但XRCC1对于已定义的SSB和具有5'-OH或5'-P末端的间隙质粒的修复并不需要，这表明XRCC1和APE2可能通过不同的机制参与SSB修复。无论是聚合酶β还是聚合酶α对已定义的SSB结构的修复都不重要。尽管如此，XRCC1对于氧化应激后DNA损伤的修复是重要的。我们的观察结果表明，XRCC1在爪蟾卵提取物氧化应激过程中对基因组完整性具有不同的作用。
Oxidative DNA damage represents one of the most abundant DNA lesions. It remains unclear how DNA repair and DNA damage response (DDR) pathways are co-ordinated and regulated following oxidative stress. While XRCC1 has been implicated in DNA repair, it remains unknown how exactly oxidative DNA damage is repaired and sensed by XRCC1. In this communication, we have demonstrated evidence that XRCC1 is dispensable for ATR-Chk1 DDR pathway following oxidative stress in Xenopus egg extracts. Whereas APE2 is essential for SSB repair, XRCC1 is not required for the repair of defined SSB and gapped plasmids with a 5'-OH or 5'-P terminus, suggesting that XRCC1 and APE2 may contribute to SSB repair via different mechanisms. Neither Polymerase beta nor Polymerase alpha is important for the repair of defined SSB structure. Nonetheless, XRCC1 is important for the repair of DNA damage following oxidative stress. Our observations suggest distinct roles of XRCC1 for genome integrity in oxidative stress in Xenopus egg extracts.