Accession Number : ADB225248
Title : Genes Involved in DNA Double-Strand Break Repair: Implications for Breast Cancer.
Descriptive Note : Annual rept. 1 Oct 95-30 Sep 96,
Corporate Author : STANFORD UNIV CA
Personal Author(s) : Chu, Gilbert
Report Date : Oct 1996
Pagination or Media Count : 50
Abstract : Ionizing radiation (IR) is both carcinogenic for breast tissue and used for treating breast cancer. In response to IR, cells undergo cell cycle arrest and repair the damaged DNA. To better combat breast cancer, the goal of this proposal has been to identify and characterize the cellular machinery required for this response. We discovered that the Ku autoantigen is deficient in mutant cells from IR complementation group 5, which is defective in repair of the DNA double-strand breaks induced by IR or by V(D)J recombination. These mutant cells are rescued by an expression vector for the Ku86 subunit and contain mutations in the Ku86 gene. Thus, Ku is required for double-strand break repair. In response to IR, cells transduce a signal that leads to accumulation of p53 and cell cycle arrest. One hypothesis is that the signal is mediated by DNA dependent protein kinase (DNA-PK), which consists of Ku as its regulatory subunit and a catalytic subunit (DNA-PKcs)'. The hypothesis was tested in primary fibroblasts from scid mice, which are deficient in DNA-PKcs. Scid cells showed normal p53 and cell cycle responses to IR. Thus, DNA-PK is not required for the induction of p53 or cell cycle arrest.
Descriptors : *REPAIR , *CARCINOGENS , *IONIZING RADIATION , *MAMMARY GLANDS , *BREAST CANCER , WARFARE , TISSUES(BIOLOGY) , CYCLES , MUTATIONS , RESPONSE , MACHINES , GENES , FIBROBLASTS , HYPOTHESES , ACCUMULATION , CELLS(BIOLOGY)
Subject Categories : Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE