Zhijiang Yan,Mathieu Delannoy,Chen Ling,Danielle Daee,Fekret Osman,Parameswary A. Muniandy,Xi Shen,Anneke B. Oostra,Hansen Du,Jurgen Steltenpool,Ti Lin,Beatrice Schuster,Chantal Décaillet,Andrzej Stasiak,Alicja Z. Stasiak,Stacie Stone,Maureen E. Hoatlin,Detlev Schindler,Christopher L. Woodcock,Hans Joenje,Ranjan Sen,Johan P. de Winter,Lei Li,Michael M. Seidman,Matthew C. Whitby,Kyungjae Myung,Angelos Constantinou,Weidong Wang See Affiliations
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FANCM and Two Histone-Fold Proteins Constitute a DNA Remodeling Complex that Maintains Genome Integrity
FANCM remodels branched DNA structures and plays essential roles in the cellular resistance to replication stress. In two papers, theWang and Meetei groups show that FANCM interacts with two histone-fold proteins, MHF1 and MHF2, which enhance the DNA repair functions of FANCM to help maintain genome stability. Preview by Thompson and Jones.
Highlights
- FANCM and two histone-fold proteins constitute a conserved DNA-remodeling complex
- The complex coordinately binds and remodels DNA such as replication forks
- The complex participates in Fanconi anemia-associated DNA damage response pathway
- The yeast version of the complex is required for recovery of blocked replication forks
Summary
- 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.