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Cryo-EM structure of translesion DNA synthesis polymerase ζ with a base pair mismatch.

ABSTRACT: The B-family multi-subunit DNA polymerase ζ (Polζ) is important for translesion DNA synthesis (TLS) during replication, due to its ability to extend synthesis past nucleotides opposite DNA lesions and mismatched base pairs. We present a cryo-EM structure of Saccharomyces cerevisiae Polζ with an A:C mismatch at the primer terminus. The structure shows how the Polζ active site responds to the mismatched duplex DNA distortion, including the loosening of key protein-DNA interactions and a fingers domain in an "open" conformation, while the incoming dCTP is still able to bind for the extension reaction. The structure of the mismatched DNA-Polζ ternary complex reveals insights into mechanisms that either stall or favor continued DNA synthesis in eukaryotes.

SUBMITTER: Malik R

PROVIDER: S-EPMC8881453 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Cryo-EM structure of translesion DNA synthesis polymerase ζ with a base pair mismatch.

Malik Radhika R Johnson Robert E RE Prakash Louise L Prakash Satya S Ubarretxena-Belandia Iban I Aggarwal Aneel K AK

Nature communications 20220225 1

The B-family multi-subunit DNA polymerase ζ (Polζ) is important for translesion DNA synthesis (TLS) during replication, due to its ability to extend synthesis past nucleotides opposite DNA lesions and mismatched base pairs. We present a cryo-EM structure of Saccharomyces cerevisiae Polζ with an A:C mismatch at the primer terminus. The structure shows how the Polζ active site responds to the mismatched duplex DNA distortion, including the loosening of key protein-DNA interactions and a fingers do ...[more]

PMID: 35217661

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