Interplay between DNA N-glycosylases/AP lyases at multiply damaged sites and biological consequences
| Autor: | Céline Giustranti, Didier Gasparutto, Marta Gonera, Evelyne Sage, Grégory Eot-Houllier |
|---|---|
| Přispěvatelé: | Génotoxicologie et cycle cellulaire (GCC), Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
Guanine
DNA Repair DNA damage DNA repair [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] CHO Cells Biology DNA Glycosylases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cricetulus hemic and lymphatic diseases Cricetinae Genetics DNA-(Apurinic or Apyrimidinic Site) Lyase Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology DNA Breaks Double-Stranded Uracil Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences [SDV.GEN]Life Sciences [q-bio]/Genetics Chinese hamster ovary cell Wild type [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology DNA-(apurinic or apyrimidinic site) lyase Molecular biology chemistry DNA glycosylase 030220 oncology & carcinogenesis DNA Cytokinesis DNA Damage |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, 2007, 35 (10), pp.3355-3366. ⟨10.1093/nar/gkm190⟩ Nucleic Acids Research, Oxford University Press, 2007, 35 (10), pp.3355-3366. ⟨10.1093/nar/gkm190⟩ |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Evidence has emerged that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. The first repair event occurring at a multiply damaged site (MDS) is of major importance and will largely contribute to the hazardousness of MDS. Here, using protein extracts from wild type or hOGG1-overexpressing Chinese hamster ovary cells, we investigated the initial incision rate at base damage and the formation of repair intermediates in various complex MDS. These MDS comprise a 1 nt gap and 3-4 base damage, including 8-oxoguanine (oG) and 5-hydroxyuracil (hU). We report a hierarchy in base excision that mainly depends on the nature and the distribution of the damage. We also show that excision at both oG and hU, and consequently DSB formation, can be modulated by hOGG1 overexpression. Anyhow, for all the MDS analyzed, DSB formation is limited, due to impaired base excision. Interestingly, repair intermediates contain a short single-stranded region carrying a potentially mutagenic base damage. This in vitro study provides new insight into the processing of MDS and suggests that repair intermediates resulting from the processing of such MDS are rather mutagenic than toxic. |
| Databáze: | OpenAIRE |
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