DNA polymerases η and κ bypass N²-guanine-O⁶-alkylguanine DNA alkyltransferase cross-linked DNA-peptides.

ABSTRACT: DNA-protein cross-links are formed when proteins become covalently trapped with DNA in the presence of exogenous or endogenous alkylating agents. If left unrepaired, they inhibit transcription as well as DNA unwinding during replication and may result in genome instability or even cell death. The DNA repair protein O⁶-alkylguanine DNA-alkyltransferase (AGT) is known to form DNA cross-links in the presence of the carcinogen 1,2-dibromoethane, resulting in G:C to T:A transversions and other mutations in both bacterial and mammalian cells. We hypothesized that AGT-DNA cross-links would be processed by nuclear proteases to yield peptides small enough to be bypassed by translesion (TLS) polymerases. Here, a 15-mer and a 36-mer peptide from the active site of AGT were cross-linked to

SUBMITTER: Ghodke PP 

PROVIDER: S-EPMC8463853 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature