Base excision repair of 7, 8-dihydro-8-oxoguanine in DNA mismatch repair proficient and mismatch repair deficient human cells
Oxidative damage is one of the most common types of DNA damage and is considered a key factor in carcinogenesis. A major form of oxidative DNA lesion is 7, 8-dihydro-8-oxoguanine (8-oxoG). The plasmid p220-12-8-oxoG:A containing the 8-oxoG located on the H-Ras codon 12 was either used to directly transform DH5á and NR12397 competent cells or after the plasmid had been incubated with HeLa, DLD1, and HCT 116 nuclear extracts. The repair efficiency of different cell lines was assessed. We also demonstrated that 40 mer Ras 8-oxoG located on H-Ras codon 12 opposite to A or C incubated with HeLa, DLD1, HCT116+3, HCT116 and LoVo nuclear extracts in BER nicking assay showed cell incision ability that uncorrelated with the levels of hMYH expression in different cell lines. We propose that the 8-oxoG:A DNA lesion located on the H-Ras codon 12 is difficult to be repaired, and that the MMR protein hMutSá may interfere with the 8-oxoG:A BER repair at codon 12. And hMutLá may contribute to the MYH in BER.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:h ras codon 12 mismatch repair deficient 7 8 dihydro oxoguanine proficient base excision human cancer cell
Date of Publication:01/01/2007