Kinetic Analysis of the Effect of N-Terminal Acetylation on Thymine DNA Glycosylase.

ABSTRACT: Thymine DNA glycosylase (TDG) is tasked with initiating DNA base excision repair by recognizing and removing T, U, the chemotherapeutic 5-fluorouracil (5-FU), and many other oxidized and halogenated pyrimidine bases. TDG contains a long, unstructured N-terminus that contains four known sites of acetylation: lysine (K) residues 59, 83, 84, and 87. Here, K to glutamine (Q) mutants are used as acetyl-lysine (AcK) analogues to probe the effect of N-terminal acetylation on the kinetics of TDG. We find that mimicking acetylation affects neither the maximal single-turnover rate k_max nor the turnover rate k_TO, indicating that the steps after initial binding, through chemistry and product release, are not affected. Under subsaturating conditions, ho

SUBMITTER: Tarantino ME 

PROVIDER: S-EPMC9117521 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature