期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
卷 41, 期 -, 页码 53-77出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.pharmtox.41.1.53
关键词
topoisomerase; camptothecin; apoptosis; ubiquitin; SUMO
资金
- NCI NIH HHS [CA39662, CA77433] Funding Source: Medline
- NIGMS NIH HHS [GM27731] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA039662, R01CA077433] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM027731] Funding Source: NIH RePORTER
DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However; they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topoisomerase poisons, acidic pH, and oxidative stresses) can convert DNA topoisomerases into DNA-breaking nucleases, resulting in cell death and/or genomic instability. The importance of topoisomerase-mediated DNA cleavage in tumor cell death and carcinogenesis has been recognized. This review focuses on recent findings concerning the molecular mechanisms of the stress responses to ropoisomerase-mediated DNA damage. The involvement of ubiquitin/26S proteasome and SUMO/UBC9 in these processes, as well as the role of topoisomerase cleavable complexes in apoptotic cell death are discussed.
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