title: FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein.
abstract: The BRCA1 associated C-terminal helicase (BACH1, designated FANCJ) is implicated in the chromosomal instability genetic disorder Fanconi anemia (FA) and hereditary breast cancer. A critical role of FANCJ helicase may be to restart replication as a component of downstream events that occur during the repair of DNA cross-links or double-strand breaks. We investigated the potential interaction of FANCJ with replication protein A (RPA), a single-stranded DNA-binding protein implicated in both DNA replication and repair. FANCJ and RPA were shown to coimmunoprecipitate most likely through a direct interaction of FANCJ and the RPA70 subunit. Moreover, dependent on the presence of BRCA1, FANCJ colocalizes with RPA in nuclear foci after DNA damage. Our data are consistent with a model in which FANCJ associates with RPA in a DNA damage-inducible manner and through the protein interaction RPA stimulates FANCJ helicase to better unwind duplex DNA substrates. These findings identify RPA as the first regulatory partner of FANCJ. The FANCJ-RPA interaction is likely to be important for the role of the helicase to more efficiently unwind DNA repair intermediates to maintain genomic stability.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD 21224, USA.
authors.forename: Rigu
authors.initials: R
authors.lastname: Gupta
authors.forename: Sudha
authors.initials: S
authors.lastname: Sharma
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sommers
authors.forename: Mark K
authors.initials: MK
authors.lastname: Kenny
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Cantor
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brosh
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics*; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D051716:Replication Protein A / Q000378:metabolism*
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D034741:RNA, Small Interfering; D051716:Replication Protein A; D004265:DNA Helicases