Vasil'eva I A, Moor N A, Lavrik O I
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia.
Dokl Biochem Biophys. 2019 Nov;489(1):357-361. doi: 10.1134/S1607672919060012. Epub 2020 Mar 4.
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.
首次研究了XRCC1蛋白氧化对聚（ADP - 核糖）聚合酶（PARP1和PARP2）催化的蛋白质修饰的影响。作为支架蛋白发挥作用的XRCC1、PARP1和PARP2负责协调对最常见DNA损伤的多步修复。我们发现，XRCC1氧化会降低其ADP - 核糖基化效率以及对聚（ADP - 核糖）的蛋白亲和力。在能够与XRCC1形成稳定复合物的DNA聚合酶β（Polβ）存在的情况下，各种XRCC1形式的ADP - 核糖修饰会增强。氧化抑制了XRCC1及其与Polβ的复合物对PARP1和PARP2自身修饰的抑制作用，这可能会提高修复效率。本研究结果表明，XRCC1氧化在蛋白质聚（ADP - 核糖基）化水平的精细调节及其在DNA修复中的协调功能中发挥作用。
