How asymmetric DNA replication achieves symmetrical fidelity.

Autor: Zhou ZX; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., Lujan SA; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., Burkholder AB; Integrative Bioinformatics Support Group, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., St Charles J; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., Dahl J; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., Farrell CE; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., Williams JS; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA., Kunkel TA; Genome Integrity & Structural Biology Laboratory, NIH/NIEHS, DHHS, Research Triangle Park, Durham, NC, USA. kunkel@niehs.nih.gov.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2021 Dec; Vol. 28 (12), pp. 1020-1028. Date of Electronic Publication: 2021 Dec 09.
DOI: 10.1038/s41594-021-00691-6
Abstrakt: Accurate DNA replication of an undamaged template depends on polymerase selectivity for matched nucleotides, exonucleolytic proofreading of mismatches, and removal of remaining mismatches via DNA mismatch repair (MMR). DNA polymerases (Pols) δ and ε have 3'-5' exonucleases into which mismatches are partitioned for excision in cis (intrinsic proofreading). Here we provide strong evidence that Pol δ can extrinsically proofread mismatches made by itself and those made by Pol ε, independently of both Pol δ's polymerization activity and MMR. Extrinsic proofreading across the genome is remarkably efficient. We report, with unprecedented accuracy, in vivo contributions of nucleotide selectivity, proofreading, and MMR to the fidelity of DNA replication in Saccharomyces cerevisiae. We show that extrinsic proofreading by Pol δ improves and balances the fidelity of the two DNA strands. Together, we depict a comprehensive picture of how nucleotide selectivity, proofreading, and MMR cooperate to achieve high and symmetrical fidelity on the two strands.
(© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)
Databáze: MEDLINE
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