A cancer-associated point mutation disables the steric gate of human PrimPol.

ABSTRACT: PrimPol is a human primase/polymerase specialized in re-starting stalled forks by repriming beyond lesions such as pyrimidine dimers, and replication-perturbing structures including G-quadruplexes and R-loops. Unlike most conventional primases, PrimPol proficiently discriminates against ribonucleotides (NTPs), being able to start synthesis using deoxynucleotides (dNTPs), yet the structural basis and physiological implications for this discrimination are not understood. In silico analyses based on the three-dimensional structure of human PrimPol and related enzymes enabled us to predict a single residue, Tyr¹⁰⁰, as the main effector of sugar discrimination in human PrimPol and a change of Tyr¹⁰⁰ to histidine to boost the efficiency of NTP incorporation. We show here th

SUBMITTER: Diaz-Talavera A 

PROVIDER: S-EPMC6362072 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature