Diverse roles of RAD18 and Y-family DNA polymerases in tumorigenesis
| Autor: | Satoshi Tateishi, Igor B. Rogozin, Yang Yang, Vyacheslav Yurchenko, Anastasia Zlatanou, Yanzhe Gao, Cyrus Vaziri |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
trans-lesion synthesis (TLS)
0301 basic medicine Carcinogenesis DNA polymerase DNA damage Ubiquitin-Protein Ligases Review DNA-Directed DNA Polymerase medicine.disease_cause 03 medical and health sciences Neoplasms medicine cancer Humans Molecular Biology Polymerase Genetics Xeroderma Pigmentosum RAD18 biology Genome Human Mutagenesis DNA replication Cell Biology Neoplasm Proteins 3. Good health Ubiquitin ligase DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Multigene Family genome maintenance Cancer cell biology.protein Signal Transduction Developmental Biology |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2018.1456296 |
| Popis: | Mutagenesis is a hallmark and enabling characteristic of cancer cells. The E3 ubiquitin ligase RAD18 and its downstream effectors, the ‘Y-family’ Trans-Lesion Synthesis (TLS) DNA polymerases, confer DNA damage tolerance at the expense of DNA replication fidelity. Thus, RAD18 and TLS polymerases are attractive candidate mediators of mutagenesis and carcinogenesis. The skin cancer-propensity disorder xeroderma pigmentosum-variant (XPV) is caused by defects in the Y-family DNA polymerase Pol eta (Polη). However it is unknown whether TLS dysfunction contributes more generally to other human cancers. Recent analyses of cancer genomes suggest that TLS polymerases generate many of the mutational signatures present in diverse cancers. Moreover biochemical studies suggest that the TLS pathway is often reprogrammed in cancer cells and that TLS facilitates tolerance of oncogene-induced DNA damage. Here we review recent evidence supporting widespread participation of RAD18 and the Y-family DNA polymerases in the different phases of multi-step carcinogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|