FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein
Department of Cancer Biology
Basic-Leucine Zipper Transcription Factors; Cell Line; DNA Damage; DNA Helicases; DNA-Binding Proteins; Fanconi Anemia; Fanconi Anemia Complementation Group Proteins; Humans; Kinetics; Mutation; Protein Binding; RNA, Small Interfering; Replication Protein A
Cancer Biology | Neoplasms
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.
DOI of Published Version
Blood. 2007 Oct 1;110(7):2390-8. Epub 2007 Jun 27. Link to article on publisher's site
Gupta, Rigu; Sharma, Sudha; Sommers, Joshua A.; Kenny, Mark K.; Cantor, Sharon B.; and Brosh, Robert M., "FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein" (2007). Cancer Biology Publications and Presentations. 1.