title: FANCM and FAAP24 maintain genome stability via cooperative as well as unique functions.
abstract: The DNA remodeling enzyme FANCM and its DNA-binding partner, FAAP24, constitute a complex involved in the activation of Fanconi anemia (FA) DNA damage response mechanism, but neither gene has distinct patient mutants. In this study, we created isogenic models for both FANCM and FAAP24 and investigated their integrated functions in DNA damage response. We found that FANCM and FAAP24 coordinately facilitate FA pathway activation and suppress sister chromatid exchange. Importantly, we show that FANCM and FAAP24 possess nonoverlapping functions such that FAAP24 promotes ATR-mediated checkpoint activation particularly in response to DNA crosslinking agents, whereas FANCM participates in recombination-independent interstrand crosslink repair by facilitating recruitment of lesion incision activities, which requires its translocase activity. Our data suggest that FANCM and FAAP24 play multiple, while not fully epistatic, roles in maintaining genomic integrity.
authors: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yucai
authors: Y
authors: Wang
authors: Justin W
authors: JW
authors: Leung
authors: Yingjun
authors: Y
authors: Jiang
authors: Megan G
authors: MG
authors: Lowery
authors: Huong
authors: H
authors: Do
authors: Karen M
authors: KM
authors: Vasquez
authors: Junjie
authors: J
authors: Chen
authors: Weidong
authors: W
authors: Wang
authors: Lei
authors: L
authors: Li
mesh_terms: D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins; D015894:Genome, Human; D042822:Genomic Instability; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans
chemical_list: D004268:DNA-Binding Proteins; C518296:FAAP24 protein, human; D051856:Fanconi Anemia Complementation Group Proteins; D004247:DNA; C518295:FANCM protein, human; D004265:DNA Helicases