Homozygous substitution of threonine 191 by proline in polymerase η causes Xeroderma pigmentosum variant.

ABSTRACT: DNA polymerase eta (Polη) is the only translesion synthesis polymerase capable of error-free bypass of UV-induced cyclobutane pyrimidine dimers. A deficiency in Polη function is associated with the human disease Xeroderma pigmentosum variant (XPV). We hereby report the case of a 60-year-old woman known for XPV and carrying a Polη Thr191Pro variant in homozygosity. We further characterize the variant in vitro and in vivo, providing molecular evidence that the substitution abrogates polymerase activity and results in UV sensitivity through deficient damage bypass. This is the first functional molecular characterization of a missense variant of Polη, whose reported pathogenic variants have thus far been loss of function truncation or frameshift mutations. Our work allows the upgrading of Polη

SUBMITTER: Ricciardiello R 

PROVIDER: S-EPMC10784498 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature