Aphidicolin-sensitive DNA repair synthesis in human fibroblasts damaged with bleomycin is distinct from UV-induced repair.

Abstract:

:Human fibroblasts repair DNA damaged by bleomycin through both short-patch and long-patch pathways, mediated by an aphidicolin-resistant (beta) and aphidicolin-sensitive (delta) DNA polymerase respectively (DiGiuseppe, J.A. and Dresler, S.L. (1989) Biochemistry, 28, 9515-9520). Despite certain similarities, aphidicolin-sensitive repair synthesis induced by bleomycin can be distinguished genetically and biochemically from that elicited by UV radiation. Permeable xeroderma pigmentosum fibroblasts of complementation groups A and G, completely deficient in UV-induced repair, display aphidicolin-sensitive repair synthesis dependent upon dose of bleomycin. Furthermore, the ribonucleotide dependence of long-patch repair induced by bleomycin differs from that of UV repair with respect to substrate specificity and apparent Km for ATP. This novel ATPase activity mediates a step prior to polymerization. By contrast, short-patch repair synthesis does not require ATP. These data suggest that, in addition to short-patch repair, human cells possess two distinct long-patch excision repair pathways. We propose that these pathways represent strand-break, base and nucleotide excision repair respectively.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

DiGiuseppe JA,Hunting DJ,Dresler SL

doi

10.1093/carcin/11.6.1021

subject

Has Abstract

pub_date

1990-06-01 00:00:00

pages

1021-6

issue

6

eissn

0143-3334

issn

1460-2180

journal_volume

11

pub_type

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