The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes

Qi Zhao, Dorina Saro, Aristidis Sachpatzidis, Thiyam Ramsing Singh, Daniel Schlingman, Xiao-Feng Zheng, Andrew Mack, Miaw-Sheue Tsai, Simon Mochrie, Lynne Regan, Amom Ruhikanta Meetei, Patrick Sung () and Yong Xiong ()
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Qi Zhao: Yale University School of Medicine
Dorina Saro: Yale University School of Medicine
Aristidis Sachpatzidis: Yale University School of Medicine
Thiyam Ramsing Singh: Cincinnati Children’s Research Foundation and University of Cincinnati College of Medicine
Daniel Schlingman: Yale University School of Medicine
Xiao-Feng Zheng: Yale University School of Medicine
Andrew Mack: Yale University
Miaw-Sheue Tsai: Lawrence Berkeley National Laboratory
Simon Mochrie: Yale University
Lynne Regan: Yale University School of Medicine
Amom Ruhikanta Meetei: Cincinnati Children’s Research Foundation and University of Cincinnati College of Medicine
Patrick Sung: Yale University School of Medicine
Yong Xiong: Yale University School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract The conserved MHF1–MHF2 (MHF) complex functions in the activation of the Fanconi anaemia pathway of the DNA damage response, in regulating homologous recombination, and in DNA replication fork maintenance. MHF facilitates the processing of multiple types of branched DNAs by the DNA translocase FANCM. Here we report the crystal structure of a human MHF–DNA complex that reveals the DNA-binding mode of MHF. The structure suggests that MHF prefers branched DNA over double-stranded DNA because it engages two duplex arms. Biochemical analyses verify that MHF preferentially engages DNA forks or various four-way junctions independent of the junction-site structure. Furthermore, genetic experiments provide evidence that the observed DNA-binding interface of MHF is important for cellular resistance to DNA damage. These results offer insights into how the MHF complex recognizes branched DNA and stimulates FANCM activity at such a structure to promote genome maintenance.

Date: 2014
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DOI: 10.1038/ncomms3987

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