Current Women`s Health Reviews

John Yeh  
Harvard Medical School 
Department of Obstetrics and Gynecology
Massachusetts General Hospital
Boston, MA
USA

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Double Strand Break Repair Activities of p53 as Potential Tumor Suppressor Function Counteracting Mammary Tumor Development

Author(s): Lisa Wiesmuller, Rolf Kreienberg.

Abstract:

Correct repair of DNA double strand breaks (DSBs) is central to the maintenance of the genome integrity, since errors give rise to translocations, deletions, duplications, and expansions, thereby accelerating the multistep process of tumorigenesis. Altered DSB repair activities have been closely linked to the development of both inherited and sporadic breast carcinomas, as indicated by frequent mutations or abnormal expression of DSB repair-related genes. Mammary epithelium appears particularly dependent on proper p53 function as indicated by the high frequency of TP53 mutations in sporadic breast cancers and the high incidence of breast cancer among Li-Fraumeni syndrome patients with mutated p53. Convergent studies demonstrated that p53 regulates recombinative DSB repair independently of classic tumor suppressor functions in transactivating target genes that are implicated in growth control or apoptosis. Moreover, physical and genetic links were established between p53 and recombination factors, such as Rad51, BRCA1 and BRCA2. Mechanistically, p53 restrains DNA exchange events involving imperfectly homologous sequences, thereby suppressing error-prone genome rearrangements. p53 as a DNA repair factor may, therefore, significantly contribute to the suppression of mammary tumor development, which is supported by the observation that the functional status of p53 as a tumor suppressor closely parallels its regulatory activities in recombination.

Keywords: Breast cancer, double strand break repair, Li-Fraumeni, p53, recombination

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Article Details

VOLUME: 2
ISSUE: 2
Year: 2006
Page: [133 - 143]
Pages: 11
DOI: 10.2174/157340406776931052
Price: $58