title: FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks.
abstract: FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Rohleder
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institute of Health, Baltimore, Maryland, MD 21224, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institute of Health, Baltimore, Maryland, MD 21224, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kuper
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, 38042 Grenoble, France Unit for Virus Host-Cell Interactions, Univ. Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, 38042 Grenoble, France Faculty of Natural sciences, Keele University, Staffordshire ST5 5BG, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Round
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institute of Health, Baltimore, Maryland, MD 21224, USA seidmanm@grc.nia.nih.gov.
authors.forename: Michael
authors.initials: M
authors.lastname: Seidman
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institute of Health, Baltimore, Maryland, MD 21224, USA wangw@grc.nia.nih.gov.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, D-97080 Würzburg, Germany caroline.kisker@virchow.uni-wuerzburg.de.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kisker
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D017124:Conserved Sequence; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D013312:Stress, Physiological; D013822:Thermoplasma / Q000201:enzymology
chemical_list: D019843:Archaeal Proteins; D018809:Proliferating Cell Nuclear Antigen; C518295:FANCM protein, human; D004265:DNA Helicases
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