Abstract

The influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP-ribose)polymerases (PARP1 and PARP2) was studied for the first time. XRCC1, PARP1, and PARP2, functioning as scaffold proteins, are responsible for coordination of multistep repair of most abundant DNA lesions. We showed that the XRCC1 oxidation reduces the efficiency of its ADP-ribosylation and the protein affinity for poly(ADP-ribose). The ADP-ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase β (Polβ), capable of forming a stable complex with XRCC1. Oxidation suppresses the inhibitory effect of XRCC1 and its complex with Polβ on the automodification of PARP1 and PARP2, which may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 plays a role in fine regulation of poly(ADP-ribosyl)ation levels of proteins and their coordinating functions in DNA repair.

中文翻译：

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XRCC1蛋白的氧化在调节哺乳动物DNA修复过程中的作用。

摘要

首次研究了XRCC1蛋白质氧化对聚（ADP-核糖）聚合酶（PARP1和PARP2）催化的蛋白质修饰的影响。XRCC1，PARP1和PARP2充当支架蛋白，负责协调最丰富的DNA损伤的多步修复。我们表明，XRCC1氧化降低了其ADP-核糖基化的效率以及对聚ADP-核糖的蛋白质亲和力。在DNA聚合酶β（Polβ）的存在下，各种XRCC1形式的ADP核糖修饰得到增强，该聚合酶能够与XRCC1形成稳定的复合物。氧化抑制XRCC1及其与Polβ的复合物对PARP1和PARP2的自修饰的抑制作用，这可能会提高修复效率。