G1 AND G2 CHECKPOINTS IN IRRADIATED CELLS

辐照细胞中的 G1 和 G2 检查点

• 批准号: 6172737
• 负责人: JOHN L REDPATH
• 金额: $ 24.59万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6172737
• 关键词: DNA damage; apoptosis; biological signal transduction; cell cycle; chromosome aberrations; cyclin dependent kinase; cyclins; enzyme activity; flow cytometry; gene expression; gene mutation; human tissue; integrins; ionizing radiation; mitogen activated protein kinase; molecular genetics; neoplastic cell; oncoprotein p21; p53 gene /protein; protein structure function; radiation genetics; radiation sensitivity; tissue /cell culture; tumor suppressor genes; tumor suppressor proteins

Studies are proposed to gain insight into molecular genetic mechanisms underlying the processing of radiation damage and the consequences of that processing. Preliminary studies with a pair of isogeneic human fibrosarcoma cell lines differing only in their p53 status have resulted in the following observations: 1) The G1 and G2 checkpoints appear to have a certain redundancy, 2) The G2 checkpoint appears to have both p53-dependent and - independent components, and 3) The proto-oncogene stathmin appears to alter p53-mediated cell cycle arrest. Experiments are proposed using synchronized cell populations to investigate the role of G1 and G2 checkpoints in chromosome aberration induction, clonogenic survival, mutation induction, and the kinetics of cell cycle progression, all following ionizing irradiation. These experiments should provide information on the impact of cell cycle checkpoints on radiation-induced cellular lethality and genetic instability. Investigations into the mechanism underlying the prolonged G1 arrest in normal human diploid skin fibroblasts have the potential to further elucidate the role of various steps in the integrin signal transduction pathway in influencing radiation-induced cell cycle arrest and genetic stability.

建议进行研究以深入了解分子遗传机制