Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair.

Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair.
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XRCC1募集对单链断裂和基础切除修复的不同时空模式和PARP依赖性。

DOI:
10.1093/nar/gkt025
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发表时间:
2013-03-01
影响因子:
14.9
通讯作者:
Radicella JP
Radicella JP
中科院分区:
生物学2区
文献类型:
--
作者:
Campalans A;Kortulewski T;Amouroux R;Menoni H;Vermeulen W;Radicella JP

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碱基和碱基修饰位点的单链断裂修复(SSBR)和碱基切除修复(BER)共享多个参与者。其中包括XRCC1,这是一种基本的支架蛋白,没有酶活性,是协调两条途径所必需的。XRCC1由PARP-1招募到SSBR,负责最初的中断识别。XRCC1对误码率的招募仍然知之甚少。在这里,我们通过使用局部和全局诱导DNA氧化碱基损伤来表明,XRCC1参与BER复合体可以通过几个标准将其与SSBR中的参与区分开来。我们首先证明了XRCC1招募到BER独立于PARP。其次,与SSBR复合体在全球损伤诱导后几分钟内组装不同,XRCC1在BER斑块中检测到的时间较晚,动力学与氧化碱基的修复一致。第三,虽然与SSBR相关的含XRCC1的焦点同时在Eu-和异染色质结构域中形成,但BER复合体组装在基本上不包括异染色质的斑块中,并在那里检测到氧化的碱基。
Single-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1, responsible for the initial recognition of the break. The recruitment of XRCC1 to BER is still poorly understood. Here we show by using both local and global induction of oxidative DNA base damage that XRCC1 participation in BER complexes can be distinguished from that in SSBR by several criteria. We show first that XRCC1 recruitment to BER is independent of PARP. Second, unlike SSBR complexes that are assembled within minutes after global damage induction, XRCC1 is detected later in BER patches, with kinetics consistent with the repair of oxidized bases. Third, while XRCC1-containing foci associated with SSBR are formed both in eu- and heterochromatin domains, BER complexes are assembled in patches that are essentially excluded from heterochromatin and where the oxidized bases are detected.
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