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FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks

Florian Rohleder1, Jing Huang2, Yutong Xue3

  • 1Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, D-97080 Würzburg, Germany.

Nucleic Acids Research
|January 31, 2016
PubMed

Insights

FANCM, a DNA repair enzyme, interacts with proliferating cell nuclear antigen (PCNA) during replication stress. This interaction is crucial for traversing DNA interstrand crosslinks and activating the Fanconi anemia pathway.

Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Cellular Stress Response

Background:

  • FANCM is a key enzyme in DNA repair, particularly for Fanconi anemia pathway activation.
  • Its role in facilitating replication traverse of DNA interstrand crosslinks is established, but its interaction with replication machinery is unclear.

Purpose of the Study:

  • To elucidate the interaction mechanism between FANCM and the replication machinery.
  • To understand how FANCM facilitates replication traverse of DNA interstrand crosslinks.

Main Methods:

  • Investigated the interaction between FANCM and proliferating cell nuclear antigen (PCNA) using its archaeal homolog Hef.
  • Utilized a conserved PIP-box motif for interaction studies and analyzed a mutated FANCM variant.

Main Results:

  • FANCM and Hef interact with PCNA via a conserved PIP-box.
  • This interaction is enhanced by replication stress in human FANCM.
  • A PIP-box mutated FANCM variant showed defects in interstrand crosslink traverse and FANCD2 monoubiquitination.

Conclusions:

  • A conserved interaction between FANCM and PCNA is revealed, occurring during replication stress.
  • This FANCM-PCNA interaction is essential for aiding replication machinery in traversing DNA interstrand crosslinks before post-replication repair.

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