Gadd45 Mediates the BRCA1-Induced Cell Cycle Arrest
Abstract
Breast cancer is the most frequent malignancy in women. More than half of the hereditary human breast cancer can be attributed to mutations in the breast susceptibility gene BRCA1 (1-3). BRCA1 has been implicated in cellular response to DNA damage, including cell cycle checkpoints, apoptosis and DNA repair (4-10). These biological events are thought o maintain genomic stability. Deregulation of genomic fidelity is closely associated with malignant transformation and tumorigenesis. However, the molecular mechanism by which BRCA1 plays a role in maintaining genomic integrity remains to be elucidated. This is to define the molecular pathway, which mediates BRCA1's role in the control of cell cycle G2-M checkpoint. The proposed studies will provide the understanding of how BRCA1 participates in maintenance of genomic stability and prevents the onset of breast cancer, as well as provide the insight to development of novel new anticancer drugs. Our previous findings indicate that BRCAl transcriptionally activates Gadd45, a p53-regulated and DNA damage-inducible gene that may play an important role in cell cycle G2-M checkpoints, apoptosis and DNA repair in response to DNA damage (11-17). Therefore, we speculated that the role of BRCA1 in cell cycle G2-M checkpoint might be mediated through Gadd45. Therefore, two major tasks have been proposed in this study. (1). To define the role Gadd45 in BRCAl-induced cell cycle G2-M arrest. (2). To determine the biochemical and molecular mechanism by which BRCAl regulates Gadd45.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA431787
Entities
People
- Qimin Zhan
Organizations
- University of Pittsburgh