{"title":"DNA聚合酶β在癌症中的作用。","authors":"Danielle L Sawyer, Joann B Sweasy","doi":"10.1615/CritRevOncog.2022043477","DOIUrl":null,"url":null,"abstract":"<p><p>DNA polymerase beta (Pol β) is a 39 kD vertebrate polymerase that lacks proofreading ability, yet still maintains a moderate fidelity of DNA synthesis. Pol β is a key enzyme that functions in the base excision repair and non-homologous end joining pathways of DNA repair. Mechanisms of fidelity for Pol β are still being elucidated but are likely to involve dynamic conformational motions of the enzyme upon its binding to DNA and deoxynucleoside triphosphates. Recent studies have linked germline and somatic variants of Pol β with cancer and autoimmunity. These variants induce genomic instability by a number of mechanisms, including error-prone DNA synthesis and accumulation of single nucleotide gaps that lead to replication stress. Here, we review the structure and function of Pol β, and we provide insights into how structural changes in Pol β variants may contribute to genomic instability, mutagenesis, disease, cancer development, and impacts on treatment outcomes.</p>","PeriodicalId":35617,"journal":{"name":"Critical Reviews in Oncogenesis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"DNA Polymerase β in the Context of Cancer.\",\"authors\":\"Danielle L Sawyer, Joann B Sweasy\",\"doi\":\"10.1615/CritRevOncog.2022043477\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>DNA polymerase beta (Pol β) is a 39 kD vertebrate polymerase that lacks proofreading ability, yet still maintains a moderate fidelity of DNA synthesis. Pol β is a key enzyme that functions in the base excision repair and non-homologous end joining pathways of DNA repair. Mechanisms of fidelity for Pol β are still being elucidated but are likely to involve dynamic conformational motions of the enzyme upon its binding to DNA and deoxynucleoside triphosphates. Recent studies have linked germline and somatic variants of Pol β with cancer and autoimmunity. These variants induce genomic instability by a number of mechanisms, including error-prone DNA synthesis and accumulation of single nucleotide gaps that lead to replication stress. Here, we review the structure and function of Pol β, and we provide insights into how structural changes in Pol β variants may contribute to genomic instability, mutagenesis, disease, cancer development, and impacts on treatment outcomes.</p>\",\"PeriodicalId\":35617,\"journal\":{\"name\":\"Critical Reviews in Oncogenesis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Oncogenesis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1615/CritRevOncog.2022043477\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Oncogenesis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1615/CritRevOncog.2022043477","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
DNA polymerase beta (Pol β) is a 39 kD vertebrate polymerase that lacks proofreading ability, yet still maintains a moderate fidelity of DNA synthesis. Pol β is a key enzyme that functions in the base excision repair and non-homologous end joining pathways of DNA repair. Mechanisms of fidelity for Pol β are still being elucidated but are likely to involve dynamic conformational motions of the enzyme upon its binding to DNA and deoxynucleoside triphosphates. Recent studies have linked germline and somatic variants of Pol β with cancer and autoimmunity. These variants induce genomic instability by a number of mechanisms, including error-prone DNA synthesis and accumulation of single nucleotide gaps that lead to replication stress. Here, we review the structure and function of Pol β, and we provide insights into how structural changes in Pol β variants may contribute to genomic instability, mutagenesis, disease, cancer development, and impacts on treatment outcomes.
期刊介绍:
The journal is dedicated to extensive reviews, minireviews, and special theme issues on topics of current interest in basic and patient-oriented cancer research. The study of systems biology of cancer with its potential for molecular level diagnostics and treatment implies competence across the sciences and an increasing necessity for cancer researchers to understand both the technology and medicine. The journal allows readers to adapt a better understanding of various fields of molecular oncology. We welcome articles on basic biological mechanisms relevant to cancer such as DNA repair, cell cycle, apoptosis, angiogenesis, tumor immunology, etc.