Alterations in DNA repair lead to genomic instability and higher risk of cancer. DNA base excision repair (BER) corrects damaged bases, apurinic sites, and single-strand DNA breaks. Here, a regulatory mechanism for DNA polymerase beta (Pol beta) is described. Pol beta was found to form a complex with the protein arginine methyltransferase 6 (PRMT6) and was specifically methylated in vitro and in vivo. Methylation of Pol beta by PRMT6 strongly stimulated DNA polymerase activity by enhancing DNA binding and processivity, while single nucleotide insertion and dRP-lyase activity were not affected. Two residues, R83 and R152, were identified in Pol beta as the sites of methylation by PRMT6. Genetic complementation of Pol beta knockout cells with R83/152K mutant revealed the importance of these residues for the cellular resistance to DNA alkylating agent. Based on our findings, we propose that PRMT6 plays a role as a regulator of BER.

中文翻译：

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精氨酸甲基化调节DNA聚合酶β。

DNA修复中的改变导致基因组不稳定和更高的癌症风险。DNA碱基切除修复（BER）可以纠正受损的碱基，无嘌呤位点和单链DNA断裂。在此，描述了DNA聚合酶β（Pol beta）的调节机制。发现Polβ与精氨酸甲基转移酶6（PRMT6）形成复合物，并在体外和体内被甲基化。PRMT6对Polβ的甲基化通过增强DNA结合力和合成能力来强烈刺激DNA聚合酶活性，而单核苷酸插入和dRP-裂合酶活性则不受影响。在Pol beta中鉴定出两个残基R83和R152作为PRMT6的甲基化位点。具有R83 / 152K突变体的Polβ基因敲除细胞的遗传互补揭示了这些残基对于细胞对DNA烷基化剂的抗性至关重要。根据我们的发现，我们建议PRMT6充当BER的调节者。