Tumor cell death induced by topoisomerase-targeting drugs.

Abstract:

: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 topoisomerase-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.

authors

Li TK,Liu LF

doi

10.1146/annurev.pharmtox.41.1.53

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

53-77

eissn

0362-1642

issn

1545-4304

pii

41/1/53

journal_volume

41

pub_type

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