Structures of LIG1 active site mutants reveal the importance of DNA end rigidity for mismatch discrimination.

ABSTRACT: ATP-dependent DNA ligases catalyze phosphodiester bond formation in the conserved three-step chemical reaction of nick sealing. Human DNA ligase I (LIG1) finalizes almost all DNA repair pathways following DNA polymerase-mediated nucleotide insertion. We previously reported that LIG1 discriminates mismatches depending on the architecture of the 3'-terminus at a nick, however the contribution of conserved active site residues to faithful ligation remains unknown. Here, we comprehensively dissect the nick DNA substrate specificity of LIG1 active site mutants carrying Ala(A) and Leu(L) substitutions at Phe(F)635 and Phe(F)F872 residues and show completely abolished ligation of nick DNA substrates with all 12 non-canonical mismatches. LIG1^EE/AA structures of F635A and F872A mutants i

SUBMITTER: Gulkis M 

PROVIDER: S-EPMC10120772 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature