title: Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair.
abstract: The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of cross-linked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway.
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Justin Wai Chung
authors.initials: JW
authors.lastname: Leung
authors.forename: Yucai
authors.initials: Y
authors.lastname: Wang
authors.forename: Ka Wing
authors.initials: KW
authors.lastname: Fong
authors.forename: Michael Shing Yan
authors.initials: MS
authors.lastname: Huen
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D002869:Chromosome Aberrations; D003432:Cross-Linking Reagents / Q000737:chemistry; D004260:DNA Repair; D005199:Fanconi Anemia / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism*; D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D016685:Mitomycin / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D003432:Cross-Linking Reagents; C570807:FAAP20 protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D051856:Fanconi Anemia Complementation Group Proteins; D025801:Ubiquitin; D016685:Mitomycin