| Modification Notes |
Genes that contribute to tumorigenesis can be broadly classified as either gatekeepers or caretakers. Genes in the gatekeeper class directly regulate cell division or cell death, and their alteration results in the uncontrolled cellular proliferation that characterizes tumor cells. Genes in the caretaker class are involved in DNA metabolic processes and are responsible for maintaining the overall stability of the genome. An unusual mutator phenotype in Caenorhabditis elegans, characterized by deletions that start around the 3' end of polyguanine tracts and terminate at variable positions 5' from such tracts, results from disruption of a gene that encodes BRIP1 (also designated BACH1 or BRCA1-associated carboxy-terminal helicase-1). BRCA1 interacts in vivo with BRIP1, a member of the DEAH helicase family. BRIP1 contains the seven helicase-specific motifs that are conserved among members of the DEAH family, and the helicase domain includes a nuclear localization signal. BRIP1 is ubiquitously expressed with highest levels in testis, an expression pattern similar to that of BRCA1. BRIP1 binds directly to the BRCT repeats of BRCA1 and the BRIP1-BRCA1 complex formation contributes to a key BRCA1 activity. BRIP1 is required to resolve the secondary structures of guanine-rich DNA that occasionally form during lagging-strand DNA synthesis. Phosphorylated BRIP1/BACH1 binds directly to the BRCT domain of BRCA1. This interaction is dependent on the phosphorylation of BRIP1/BACH1 at Ser 990, and is required for DNA damage-induced checkpoint control during the G2 to M phase transition of the cell cycle. |
