Repair of and checkpoint response to topoisomerase I-mediated DNA damage.
Mutat Res
; 532(1-2): 173-203, 2003 Nov 27.
Article
em En
| MEDLINE
| ID: mdl-14643436
ABSTRACT
Topoisomerase I (Top1) catalyzes two transesterification reactions single-strand DNA cleavage and religation that are normally coupled for the relaxation of DNA supercoiling in transcribing and replicating chromatin. A variety of endogenous DNA modifications, potent anticancer drugs and carcinogens uncouple these two reactions, resulting in the accumulation of Top1 cleavage complexes. Top1 cleavage complexes damage DNA and kill cells by generating replication-mediated DNA double-strand breaks (DSBs) and by stalling transcription complexes. The repair of Top1-mediated DNA lesions involves integrated pathways that are conserved from yeasts to humans. Top1-mediated DNA damage and cell cycle checkpoint responses can be studied biochemically and genetically in yeast and human cells with known genetic defects. Defects in these repair/checkpoint pathways, which promote tumor development, explain, at least in part, the selectivity of camptothecins and other Top1 inhibitors for cancer cells.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Ciclo Celular
/
DNA Topoisomerases Tipo I
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mutat Res
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos