Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis
Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis
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DOI：
10.1093/emboj/cdg626
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发表时间：
2003-12-15
期刊：
影响因子：
11.4
通讯作者：
Friedberg, EC
中科院分区：
文献类型：
--
作者：
Guo, CX;Fischhaber, PL;Friedberg, EC
Polkappa和Rev 1是DNA聚合酶Y家族的成员，参与对复制旁路（translesion DNA synthesis，TLS）引起的DNA损伤的耐受。我们证明，小鼠Rev 1蛋白物理协会与Polkappa。我们还表明，Rev 1独立地与Rev 7（TLS聚合酶Polzeta的亚基）和其他两个Y家族聚合酶Poliota和Poleta相互作用。小鼠Polkappa、Rev 7、Poliota和Poleta各自与Rev 1的100个氨基酸C末端区域结合。此外，Rev 7直接与Polkappa竞争结合Rev 1 C末端。不考虑Rev 1和Polkappa之间的物理相互作用，通过体外引物延伸测量的每种DNA聚合酶活性不受复合物的影响，无论是在延伸正常的引物末端时，绕过单个胸腺嘧啶乙二醇损伤时，还是在延伸某些错配的引物末端时。我们的观察表明，Rev 1在介导TLS所需的DNA聚合酶之间的蛋白质-蛋白质相互作用中起作用。TLS期间这些相互作用的精确功能仍有待确定。
Polkappa and Rev1 are members of the Y family of DNA polymerases involved in tolerance to DNA damage by replicative bypass [translesion DNA synthesis (TLS)]. We demonstrate that mouse Rev1 protein physically associates with Polkappa. We show too that Rev1 interacts independently with Rev7 (a subunit of a TLS polymerase, Polzeta) and with two other Y-family polymerases, Poliota and Poleta. Mouse Polkappa, Rev7, Poliota and Poleta each bind to the same similar to100 amino acid C-terminal region of Rev1. Furthermore, Rev7 competes directly with Polkappa for binding to the Rev1 C-terminus. Notwith standing the physical interaction between Rev1 and Polkappa, the DNA polymerase activity of each measured by primer extension in vitro is unaffected by the complex, either when extending normal primer-termini, when bypassing a single thymine glycol lesion, or when extending certain mismatched primer termini. Our observations suggest that Rev1 plays a role(s) in mediating protein-protein interactions among DNA polymerases required for TLS. The precise function(s) of these interactions during TLS remains to be determined.