Increased mutability and decreased repairability of a three-lesion clustered DNA-damaged site comprised of an AP site and bi-stranded 8-oxoG lesions

Autor:	Alexandra K. Walker, Peter O'Neill, Martine E. Lomax, Robert Stabler, Siobhan Cunniffe
Rok vydání:	2014
Předmět:	DNA Bacterial Guanine DNA Repair DNA repair DNA damage CHO Cells 8-oxoG Biology medicine.disease_cause base excision repair chemistry.chemical_compound Cricetulus Cricetinae medicine Escherichia coli Animals Radiology Nuclear Medicine and imaging AP site mutagenic potential Mutation Radiological and Ultrasound Technology Clustered DNA damage Base excision repair DNA Molecular biology chemistry DNA glycosylase Original Article Nucleotide excision repair DNA Damage
Zdroj:	International Journal of Radiation Biology
ISSN:	1362-3095
Popis:	Purpose Ionizing radiation induces DNA damage, some of which are present in clusters, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. These clusters are thought to contribute to the detrimental effects of radiation, in part due to the compromised repair of clustered DNA damaged sites. Materials and methods The repair of three-lesion cluster present in oligonucleotides were determined in vitro using the hamster cell line CHO-K1 nuclear extract or purified proteins involved in base excision repair. The mutagenic potential of these clusters present in a plasmid was determined using an Escherichia coli reporter assay. Results We have shown that the repair of an abasic (AP) site within a three-lesion cluster, comprised of an AP site and bi-stranded 8-oxo-7,8-dihydroguanine (8-oxoG) lesions, is retarded compared to that of an isolated AP site in an in vitro base excision repair (BER) assay. Further, the mutation frequency of the clustered damaged site is up to three times greater than that of an isolated 8-oxoG lesion. Conclusions As a consequence of enhanced mutagenic potential of clusters, non-double-strand break (DSB) DNA damage may contribute to the detrimental effects of radiation, in addition to the effects of DSB.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f058c2ac0028cc8ca28fa857485415a https://pubmed.ncbi.nlm.nih.gov/24597750 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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