A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability.

A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability.
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DOI:
10.1016/j.molcel.2010.01.039
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发表时间:
2010-03-26
期刊:
影响因子:
16
通讯作者:
Wang W
Wang W
中科院分区:
生物学1区
文献类型:
--
作者:
Yan Z;Delannoy M;Ling C;Daee D;Osman F;Muniandy PA;Shen X;Oostra AB;Du H;Steltenpool J;Lin T;Schuster B;Décaillet C;Stasiak A;Stasiak AZ;Stone S;Hoatlin ME;Schindler D;Woodcock CL;Joenje H;Sen R;de Winter JP;Li L;Seidman MM;Whitby MC;Myung K;Constantinou A;Wang W

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FANCM重塑分支DNA结构,在细胞对DNA复制应激的反应中发挥重要作用。在这里,我们表明FANCM与组蛋白折叠异源二聚体MHF形成保守的DNA重塑复合体。我们通过FANCM发现MHF刺激DNA结合和复制叉重塑。在细胞中,FANCM和MHF被迅速招募到被DNA链间交联物阻挡的叉子上,这两种分子都是细胞抵抗这种损伤所必需的。在脊椎动物中,FANCM-MHF与Fanconi贫血(FA)核心复合体结合,促进FANCD2单偶联反应DNA损伤,并抑制姐妹染色单体交换。这些蛋白质的酵母同源物共同发挥作用,以抵抗MMS诱导的DNA损伤,并促进被阻断的复制叉处的基因转换。因此,FANCM-MHF是一种重要的DNA重塑复合体,可以保护从酵母到人类的复制叉子。
FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. Here we show that FANCM forms a conserved DNA remodeling complex with a histone-fold heterodimer, MHF. We find that MHF stimulates DNA binding and replication fork remodeling by FANCM. In the cell, FANCM and MHF are rapidly recruited to forks stalled by DNA interstrand crosslinks, and both are required for cellular resistance to such lesions. In vertebrates, FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage, and suppresses sister-chromatid exchanges. Yeast orthologs of these proteins function together to resist MMS-induced DNA damage and promote gene conversion at blocked replication forks. Thus, FANCM-MHF is an essential DNA remodeling complex that protects replication forks from yeast to human.
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