High-fidelity DNA ligation enforces accurate Okazaki fragment maturation during DNA replication.

ABSTRACT: DNA ligase 1 (LIG1, Cdc9 in yeast) finalizes eukaryotic nuclear DNA replication by sealing Okazaki fragments using DNA end-joining reactions that strongly discriminate against incorrectly paired DNA substrates. Whether intrinsic ligation fidelity contributes to the accuracy of replication of the nuclear genome is unknown. Here, we show that an engineered low-fidelity LIG1^Cdc9 variant confers a novel mutator phenotype in yeast typified by the accumulation of single base insertion mutations in homonucleotide runs. The rate at which these additions are generated increases upon concomitant inactivation of DNA mismatch repair, or by inactivation of the Fen1^Rad27 Okazaki fragment maturation (OFM) nuclease. Biochemical and structural data establish that LIG1^Cdc9 n

SUBMITTER: Williams JS 

PROVIDER: S-EPMC7817679 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature