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

Author(s)

Feltes, Bruno Cesar ; Menck, Carlos Frederico Martins

• Document type: Journal article
• Source: MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH; v. 790, p. 15-pg., 2022-07-01.

Abstract

POL eta encoded by the POLH gene, is a crucial protein for replicating damaged DNA and the most studied specialized translesion synthesis polymerases. Mutations in POL eta 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 POL eta is vast, covering dozens of different mutants, numerous crucial residues, domains, and posttranslational modifications that are essential for protein function within cells. Since POL eta 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 POL eta: from basic knowledge about critical residues and protein domains to its mutant variants, posttranslational modifications, and our current understanding of therapeutic molecules that target POL eta. Thus, this review provides lessons about POL eta's structure and gathers critical discussions and hypotheses that may contribute to understanding this protein's vital roles within the cells. (AU)

• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants