Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B.

Abstract:

:Reactive oxygen species, which are prevalent in mitochondria, cause oxidative DNA damage including the mutagenic DNA lesion 7,8-dihydroxyguanine (8-oxoG). Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, and in cancer and aging. 8-oxoG is repaired efficiently in mammalian mitochondrial DNA by enzymes in the base excision repair pathway, including the 8-oxoguanine glycosylase (OGG1), which incizes the lesion in the first step of repair. Cockayne syndrome (CS) is a segmental premature aging syndrome in humans that has two complementation groups, CSA and CSB. Previous studies showed that CSB-deficient cells have reduced capacity to repair 8-oxoG. This study examines the role of the CSB gene in regulating repair of 8-oxoG in mitochondrial DNA in human and mouse cells. 8-oxoG repair was measured in liver cells from CSB deficient mice and in human CS-B cells carrying expression vectors for wild type or mutant forms of the human CSB gene. For the first time we report that CSB stimulates repair of 8-oxoG in mammalian mitochondrial DNA. Furthermore, evidence is presented to support the hypothesis that wild type CSB regulates expression of OGG1.

journal_name

Oncogene

journal_title

Oncogene

authors

Stevnsner T,Nyaga S,de Souza-Pinto NC,van der Horst GT,Gorgels TG,Hogue BA,Thorslund T,Bohr VA

doi

10.1038/sj.onc.1205994

subject

Has Abstract

pub_date

2002-12-12 00:00:00

pages

8675-82

issue

57

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

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