PuSH - Publikationsserver des Helmholtz Zentrums München

Sagan, D. ; Müller, R. ; Kröger, C. ; Hematulin, A. ; Mörtl, S. ; Eckardt-Schupp, F.

The DNA repair protein NBS1 influences the base excision repair pathway.

Carcinogenesis 30, 408-415 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
NBS1 fulfills important functions for the maintenance of genomic stability and cellular survival. Mutations in the NBS1 (Nijmegen Breakage Syndrome 1) gene are responsible for the Nijmegen breakage syndrome (NBS) in humans. The symptoms of this disease and the phenotypes of NBS1-defective cells, especially their enhanced radiosensitivity, can be explained by an impaired DNA double-strand break-induced signaling and a disturbed repair of these DNA lesions. We now provide evidence that NBS1 is also important for cellular survival after oxidative or alkylating stress where it is required for the proper initiation of base excision repair (BER). NBS1 downregulated cells show reduced activation of poly-(adenosine diphosphate-ribose)-polymerase-1 (PARP1) following genotoxic treatment with H2O2 or methyl methanesulfonate, indicating impaired processing of damaged bases by BER as PARP1 activity is stimulated by the single-strand breaks intermediately generated during this repair pathway. Furthermore, extracts of these cells have a decreased capacity for the in vitro repair of a double-stranded oligonucleotide containing either uracil or 8-oxo-7,8-dihydroguanine to trigger BER. Our data presented here highlight for the first time a functional role for NBS1 in DNA maintenance by the BER pathway.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter strand break repair; werner-syndrome protein; ataxia-telangiectasia cells; poly(adp-ribose) polymerase-1; mre11/rad50/nbs1 complex; alzheimers-disease; damage; glycosylase; parp-1; mre11
ISSN (print) / ISBN 0143-3334
e-ISSN 1460-2180
Zeitschrift Carcinogenesis
Quellenangaben Band: 30, Heft: 3, Seiten: 408-415 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)