UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2005-12-17Keywords
AnimalsBRCA1 Protein
Basic-Leucine Zipper Transcription Factors
Fanconi Anemia
Fanconi Anemia Complementation Group Proteins
Humans
Models, Biological
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The BACH1 helicase was initially identified by its direct binding to BRCA1 and, thus, was linked to hereditary breast cancer. More recently, BACH1 was identified as the gene defective in the J complementation group of Fanconi anemia (FA). FA is a multigenetic disorder characterized by cellular sensitivity to crosslinkers and chromosome instability. Because FANCD2 monoubiquitination is intact in BACH1 deficient cells, BACH1 appears to act downstream in the FA pathway akin to BRCA2/FANCD1. Interestingly, while BRCA1 has various interactions with FA proteins it has not been identified as an FA gene. As the race to uncover the last few unknown FA complementation groups comes to an end, future work will be required to uncover how these gene products function to combat the effects of DNA damage and maintain genomic stability. In particular, it remains elusive whether BRCA1 is functionally linked to the FA pathway through its interaction with BACH1/FANCJ. This review focuses on a model for the connection of BRCA1 to BACH1 in the FA pathway. We predict that BRCA1 regulates the BACH1 helicase activity to coordinate the timely displacement of Rad51 from nucleofilaments, promoting error free repair and ultimately maintaining chromosomal integrity.Source
Cell Cycle. 2006 Jan;5(2):164-7. Epub 2006 Jan 16.