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

Author

Listed:
  • 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
    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)

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.

Suggested Citation

  • 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 & Patr, 2014. "The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms3987
    DOI: 10.1038/ncomms3987
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