Current state of knowledge of human DNA polymerase eta protein structure and disease-causing mutations.

Autor: Feltes BC; Department of Theoretical Informatics, Institute of Informatics, Department of Theoretical Informatics, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil; Department of Genetics, Institute of Bioscience, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Department of Biophysics, Institute of Bioscience, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil., Menck CFM; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Mutation research. Reviews in mutation research [Mutat Res Rev Mutat Res] 2022 Jul-Dec; Vol. 790, pp. 108436. Date of Electronic Publication: 2022 Aug 08.
DOI: 10.1016/j.mrrev.2022.108436
Abstrakt: POLη, encoded by the POLH gene, is a crucial protein for replicating damaged DNA and the most studied specialized translesion synthesis polymerases. Mutations in POLη are associated with cancer and the human syndrome xeroderma pigmentosum variant, which is characterized by extreme photosensitivity and an increased likelihood of developing skin cancers. The myriad of structural information about POLη is vast, covering dozens of different mutants, numerous crucial residues, domains, and posttranslational modifications that are essential for protein function within cells. Since POLη is key vital enzyme for cell survival, and mutations in this protein are related to aggressive diseases, understanding its structure is crucial for biomedical sciences, primarily due to its similarities with other Y-family polymerases and its potential as a targeted therapy-drug for tumors. This work provides an up-to-date review on structural aspects of the human POLη: from basic knowledge about critical residues and protein domains to its mutant variants, posttranslational modifications, and our current understanding of therapeutic molecules that target POLη. Thus, this review provides lessons about POLη's structure and gathers critical discussions and hypotheses that may contribute to understanding this protein's vital roles within the cells.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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