Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase η at atomic resolution.

ABSTRACT: Oxidatively induced DNA lesions 8,5'-cyclopurine-2'-deoxynucleosides (cdPus) are prevalent and cytotoxic by impeding DNA replication and transcription. Both the 5'R- and 5'S-diastereomers of cdPu can be removed by nucleotide excision repair; however, the 5'S-cdPu is more resistant to repair than the 5'R counterpart. Here, we report the crystal structures of human polymerase (Pol) η bypassing 5'S-8,5'-cyclo-2'-deoxyadenosine (cdA) in insertion and the following two extension steps. The cdA-containing DNA structures vary in response to the protein environment. Supported by the "molecular splint" of Pol η, the structure of 5'S-cdA at 1.75-Å resolution reveals that the backbone is pinched toward the minor groove and the adenine base is tilted. In the t

SUBMITTER: Weng PJ 

PROVIDER: S-EPMC6196489 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature