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Influence of template strandedness on in vitro replication of mutagen-damaged

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00383a011· OSTI ID:5624700

The authors analyzed the ability of DNA polymerases to bypass damage on single- and double-stranded templates. In vitro DNA synthesis was studied on UV-irradiated and polyaromatic hydrocarbon reacted (benzo(a)pyrenediol epoxide and oxiranylpyrene) double-stranded templates by a protocol involving initiation on a uniquely nicked circular double-stranded template. The template was prepared by treating single-stranded (+)M13mp2 circular strands with mutagen and then hybridizing with restricted M13 RFmp2, followed by isolation of the nicked RFII forms. The protocol permits either (+), (-), or both strands to carry lesions. They found that the rules for termination and bypass of lesions previously observed with single-stranded DNA templates also hold for double-stranded templates. Termination of synthesis occurs primarily one nucleotide 3' to the lesion in the template strand. Bypass of UV-induced lesions can be followed in a series of three partial reactions in the presence of Mn/sup 2 +/ and dGMP, which relax the specificity of nucleotide insertion and 3' ..-->.. 5' exonuclease activity, respectively. There is no evidence for greater permissivity of bypass in double-as opposed to single-stranded templates. As with single-stranded templates, purines, and preferentially deoxyadenosine (dA) are inserted opposite lesions. Lesions in the nontemplate strand elicit neither termination nor pausing. The addition of Rec A protein resulted in a measurable increase of bypass in this system.

Research Organization:
Univ. of Chicago, IL
OSTI ID:
5624700
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:9; ISSN BICHA
Country of Publication:
United States
Language:
English