Reference: Malik R, et al. (2022) Cryo-EM structure of translesion DNA synthesis polymerase ζ with a base pair mismatch. Nat Commun 13(1):1050

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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.

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Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
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Malik R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK
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