Training in Support of a Research Project Entitled Regulation of BRCA1 Function by Phosphorylation
Abstract
Mutations in the breast cancer susceptibility gene BRCAl account for 50% of familial cases, and about 2 to 5% of all cases of breast cancer. Most of the BRCAl linked tumors have undergone loss of heterozygozity at this locus, classifying BRCAl as a tumor suppressor. Substantial evidence implicates BRCAl to be involved in cellular DNA damage response and DNA repair pathways. Mouse cells deficient for Brcal show genetic instability, defective G2/M checkpoint control and reduced homologous recombination. BRCAl also interacts with proteins of the DNA repair machinery and regulates expression of p21 and GADD45 genes. However, it remains unclear how DNA damage signals are transmitted to modulate the repair function of BRCAl. Previous work from our laboratory have shown that BRCAl becomes hyperphosphorylated in a cell cycle dependent manner and in response to genotoxic insults. Here, we further investigated how this phosphorylation event contributes to the cellular function of BRCAl. Our results revealed a novel DNA damage response pathway that involves the protein kinase mutated in Ataxia telangiectasia (ATM), a BRCAl associated protein, CtIP, and BRCAl, thus providing a potential link between ATM deficiency and breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA387823
Entities
People
- Nicholas Ting
Organizations
- University of Texas Health Science Center at San Antonio