期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 22, 期 24, 页码 8635-8647出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.22.24.8635-8647.2002
关键词
-
资金
- NCI NIH HHS [CA16672, T32 CA009299, R01 CA052461, CA90270, CA75160, P50 CA090270, P30 CA016672, CA52461, CA09299, R01 CA075160] Funding Source: Medline
- NIDCR NIH HHS [R01 DE 13157, R01 DE013157] Funding Source: Medline
- NIGMS NIH HHS [R56 GM065812, R01 GM065812, GM65812-01] Funding Source: Medline
snm1 mutants of Saccharomyces cerevisiae have been shown to be specifically sensitive to DNA interstrand crosslinking agents but not sensitive to monofunctional alkylating agents, UV, or ionizing radiation. Five homologs of SNM1 have been identified in the mammalian genome and are termed SNM1, SNM1B, Artemis, ELAC2, and CPSF73. To explore the functional role of human Snm1 in response to DNA damage, we characterized the cellular distribution and dynamics of human Snm1 before and after exposure to DNA-damaging agents. Human Snm1 was found to localize to the cell nucleus in three distinct patterns. A particular cell showed diffuse nuclear staining, multiple nuclear foci, or one or two larger bodies confined to the nucleus. Upon exposure to ionizing radiation or an interstrand crosslinking agent, the number of cells exhibiting Snm1 bodies was reduced, while the population of cells with foci increased dramatically. Indirect immunofluorescence studies also indicated that the human Snm1 protein colocalized with 53BP1 before and after exposure to ionizing radiation, and a physical interaction was confirmed by coimmunoprecipitation assays. Furthermore, human Snm1 foci formed after ionizing radiation were largely coincident with foci formed by human Mre11 and to a lesser extent with those formed by BRCA1, but not with those formed by human Rad51. Finally, we mapped a region of human Snm1 of approximately 220 amino acids that was sufficient for focus formation when attached to a nuclear localization signal. Our results indicate a novel function for human Snm1 in the cellular response to double-strand breaks formed by ionizing radiation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据