The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA

J Tuo; M Müftüoglu; C Chen; P Jaruga; R R Selzer; R M Brosh; H Rodriguez; M Dizdaroglu; V A Bohr

doi:10.1074/jbc.M107888200

The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA

J Tuo, M Müftüoglu, C Chen, P Jaruga, R R Selzer, R M Brosh, H Rodriguez, M Dizdaroglu, V A Bohr

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

136 Citationer (Scopus)

Abstract

Udgivelsesdato: 2001-Dec-7

Originalsprog	Engelsk
Tidsskrift	Journal of Biological Chemistry
Vol/bind	276
Udgave nummer	49
Sider (fra-til)	45772-9
Antal sider	7
ISSN	0021-9258
DOI	https://doi.org/10.1074/jbc.M107888200
Status	Udgivet - 2001
Udgivet eksternt	Ja

Bibliografisk note

Keywords: Amino Acid Sequence; Cell Line, Transformed; Cockayne Syndrome; DNA; DNA Helicases; DNA Repair; DNA Repair Enzymes; Genome; Guanine; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Oxidative Stress

Adgang til dokumentet

10.1074/jbc.M107888200

Citationsformater

@article{6f18e230664211de8bc9000ea68e967b,

title = "The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA",

abstract = "Cockayne Syndrome (CS) is a human genetic disorder with two complementation groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled repair of DNA damage but may participate in other pathways of DNA metabolism. The present study investigated the role of different conserved helicase motifs of CSB in base excision repair. Stably transformed human cell lines with site-directed CSB mutations in different motifs within its putative helicase domain were established. We find that CSB null and helicase motif V and VI mutants had greater sensitivity than wild type cells to gamma-radiation. Whole cell extracts from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanine incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in CSB null and motif VI mutant cells than in wild type cells after exposure to gamma-radiation. We conclude that a deficiency in general genome base excision repair of selective modified DNA base(s) might contribute to CS pathogenesis. Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB phenotype, mutations in other helicase motifs do not cause this effect. The biological functions of CSB in different DNA repair pathways may be mediated by distinct functional motifs of the protein.",

author = "J Tuo and M M{\"u}ft{\"u}oglu and C Chen and P Jaruga and Selzer, {R R} and Brosh, {R M} and H Rodriguez and M Dizdaroglu and Bohr, {V A}",

note = "Keywords: Amino Acid Sequence; Cell Line, Transformed; Cockayne Syndrome; DNA; DNA Helicases; DNA Repair; DNA Repair Enzymes; Genome; Guanine; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Oxidative Stress",

year = "2001",

doi = "10.1074/jbc.M107888200",

language = "English",

volume = "276",

pages = "45772--9",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

number = "49",

}

TY - JOUR

T1 - The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA

AU - Tuo, J

AU - Müftüoglu, M

AU - Chen, C

AU - Jaruga, P

AU - Selzer, R R

AU - Brosh, R M

AU - Rodriguez, H

AU - Dizdaroglu, M

AU - Bohr, V A

N1 - Keywords: Amino Acid Sequence; Cell Line, Transformed; Cockayne Syndrome; DNA; DNA Helicases; DNA Repair; DNA Repair Enzymes; Genome; Guanine; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Oxidative Stress

PY - 2001

Y1 - 2001

N2 - Cockayne Syndrome (CS) is a human genetic disorder with two complementation groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled repair of DNA damage but may participate in other pathways of DNA metabolism. The present study investigated the role of different conserved helicase motifs of CSB in base excision repair. Stably transformed human cell lines with site-directed CSB mutations in different motifs within its putative helicase domain were established. We find that CSB null and helicase motif V and VI mutants had greater sensitivity than wild type cells to gamma-radiation. Whole cell extracts from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanine incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in CSB null and motif VI mutant cells than in wild type cells after exposure to gamma-radiation. We conclude that a deficiency in general genome base excision repair of selective modified DNA base(s) might contribute to CS pathogenesis. Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB phenotype, mutations in other helicase motifs do not cause this effect. The biological functions of CSB in different DNA repair pathways may be mediated by distinct functional motifs of the protein.

AB - Cockayne Syndrome (CS) is a human genetic disorder with two complementation groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled repair of DNA damage but may participate in other pathways of DNA metabolism. The present study investigated the role of different conserved helicase motifs of CSB in base excision repair. Stably transformed human cell lines with site-directed CSB mutations in different motifs within its putative helicase domain were established. We find that CSB null and helicase motif V and VI mutants had greater sensitivity than wild type cells to gamma-radiation. Whole cell extracts from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanine incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in CSB null and motif VI mutant cells than in wild type cells after exposure to gamma-radiation. We conclude that a deficiency in general genome base excision repair of selective modified DNA base(s) might contribute to CS pathogenesis. Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB phenotype, mutations in other helicase motifs do not cause this effect. The biological functions of CSB in different DNA repair pathways may be mediated by distinct functional motifs of the protein.

U2 - 10.1074/jbc.M107888200

DO - 10.1074/jbc.M107888200

M3 - Journal article

C2 - 11581270

SN - 0021-9258

VL - 276

SP - 45772

EP - 45779

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 49

ER -