FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein

Blood. 2007 Oct 1;110(7):2390-8. doi: 10.1182/blood-2006-11-057273. Epub 2007 Jun 27.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Line
  • DNA Damage / genetics*
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia Complementation Group Proteins / metabolism*
  • Humans
  • Kinetics
  • Mutation / genetics
  • Protein Binding
  • RNA, Small Interfering / genetics
  • Replication Protein A / metabolism*

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group Proteins
  • RNA, Small Interfering
  • Replication Protein A
  • DNA Helicases