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首页> 外文期刊>Nucleic Acids Research >FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks
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FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks

机译：FANCM与PCNA相互作用以促进DNA链间交联的复制遍历

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摘要

FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.
机译：FANCM是高度保守的DNA重塑酶，可促进Fanconi贫血DNA修复途径的激活并促进DNA链间交联的复制遍历。但是，FANCM如何与复制机制相互作用以促进遍历仍不清楚。在这里，我们显示FANCM及其嗜酸嗜热单胞菌的古同系Hef与增殖细胞核抗原（PCNA）相互作用，后者是DNA聚合酶在复制和修复中必不可少的辅助因子。相互作用通过保守的PIP盒介导;在人类FANCM中，复制压力强烈刺激它。在PIP盒中携带突变的FANCM变体在促进链间交联的复制遍历方面存在缺陷，并且在促进FANCD2贫血途径的关键步骤FANCD2单泛素化方面也无效。我们的数据揭示了复制压力期间FANCM和PCNA之间的保守相互作用模式，并表明这种相互作用对于FANCM有助于复制机在复制后修复之前穿越DNA链间交联至关重要。

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