title: FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway.
abstract: Fanconi anemia (FA) nuclear core complex is a multiprotein complex required for the functional integrity of the FA-BRCA pathway regulating DNA repair. This pathway is inactivated in FA, a devastating genetic disease, which leads to hematologic defects and cancer in patients. Here we report the isolation and characterization of a novel 20-kDa FANCA-associated protein (FAAP20). We show that FAAP20 is an integral component of the FA nuclear core complex. We identify a region on FANCA that physically interacts with FAAP20, and show that FANCA regulates stability of this protein. FAAP20 contains a conserved ubiquitin-binding zinc-finger domain (UBZ), and binds K-63-linked ubiquitin chains in vitro. The FAAP20-UBZ domain is not required for interaction with FANCA, but is required for DNA-damage-induced chromatin loading of FANCA and the functional integrity of the FA pathway. These findings reveal critical roles for FAAP20 in the FA-BRCA pathway of DNA damage repair and genome maintenance.
authors.affiliation: Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Abdullah Mahmood
authors.initials: AM
authors.lastname: Ali
authors.forename: Arun
authors.initials: A
authors.lastname: Pradhan
authors.forename: Thiyam Ramsingh
authors.initials: TR
authors.lastname: Singh
authors.forename: Changhu
authors.initials: C
authors.lastname: Du
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Kebola
authors.initials: K
authors.lastname: Wahengbam
authors.forename: Elke
authors.initials: E
authors.lastname: Grassman
authors.forename: Arleen D
authors.initials: AD
authors.lastname: Auerbach
authors.forename: Qishen
authors.initials: Q
authors.lastname: Pang
authors.forename: Amom Ruhikanta
authors.initials: AR
authors.lastname: Meetei
mesh_terms: D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein / Q000737:chemistry / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D002843:Chromatin; C570807:FAAP20 protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D051856:Fanconi Anemia Complementation Group Proteins; D025801:Ubiquitin