title: The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex.
abstract: Fanconi anaemia (FA) is an autosomal-recessive disorder characterized by genomic instability, developmental defects, DNA crosslinking agent hypersensitivity and cancer susceptibility. Somatic-cell hybrid studies have revealed five FA complementation groups (A-E; refs 4-6) displaying similar phenotypes, suggesting that FA genes are functionally related. The two cloned FA genes, FAA and FAC, encode proteins that are unrelated to each other or to other proteins in GenBank. In the current study, we demonstrate the FAA and FAC bind each other and form a complex. Protein binding correlates with the functional activity of FAA and FAC, as patient-derived mutant FAC (L554P) fails to bind FAA. Although unbound FAA and FAC localize predominantly to the cytoplasm, the FAA-FAC complex is found in similar abundance in both cytoplasm and nucleus. Our results confirm the interrelatedness of the FA genes in a pathway, suggesting the cooperation of FAA and FAC in a nuclear function.
authors.affiliation: Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. garyvkupfer@dfci.harvard.edu
authors.forename: G M
authors.initials: GM
authors.lastname: Kupfer
authors.forename: D
authors.initials: D
authors.lastname: Näf
authors.forename: A
authors.initials: A
authors.lastname: Suliman
authors.forename: M
authors.initials: M
authors.lastname: Pulsipher
authors.forename: A D
authors.initials: AD
authors.lastname: D'Andrea
mesh_terms: D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins