A panoply of errors: polymerase proofreading domain mutations in cancer
Although it has long been recognized that the exonucleolytic proofreading activity intrinsic to the replicative DNA polymerases Pol δ and Pol ε is essential for faithful replication of DNA, evidence that defective DNA polymerase proofreading contributes to human malignancy has been limited. However,...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
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Nature Research
2016
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| _version_ | 1797095100114796544 |
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| author | Rayner, E Van Gool, I Palles, C Kearsey, S Bosse, T Tomlinson, I Church, D |
| author_facet | Rayner, E Van Gool, I Palles, C Kearsey, S Bosse, T Tomlinson, I Church, D |
| author_sort | Rayner, E |
| collection | OXFORD |
| description | Although it has long been recognized that the exonucleolytic proofreading activity intrinsic to the replicative DNA polymerases Pol δ and Pol ε is essential for faithful replication of DNA, evidence that defective DNA polymerase proofreading contributes to human malignancy has been limited. However, recent studies have shown that germline mutations in the proofreading domains of Pol δ and Pol ε predispose to cancer, and that somatic Pol ε proofreading domain mutations occur in multiple sporadic tumours, where they underlie a phenotype of 'ultramutation' and favourable prognosis. In this Review, we summarize the current understanding of the mechanisms and consequences of polymerase proofreading domain mutations in human malignancies, and highlight the potential utility of these variants as novel cancer biomarkers and therapeutic targets. |
| first_indexed | 2024-03-07T04:23:14Z |
| format | Journal article |
| id | oxford-uuid:cbbc678a-6f1c-415e-82c9-e664369e8097 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T04:23:14Z |
| publishDate | 2016 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:cbbc678a-6f1c-415e-82c9-e664369e80972022-03-27T07:17:03ZA panoply of errors: polymerase proofreading domain mutations in cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cbbc678a-6f1c-415e-82c9-e664369e8097Symplectic Elements at OxfordNature Research2016Rayner, EVan Gool, IPalles, CKearsey, SBosse, TTomlinson, IChurch, DAlthough it has long been recognized that the exonucleolytic proofreading activity intrinsic to the replicative DNA polymerases Pol δ and Pol ε is essential for faithful replication of DNA, evidence that defective DNA polymerase proofreading contributes to human malignancy has been limited. However, recent studies have shown that germline mutations in the proofreading domains of Pol δ and Pol ε predispose to cancer, and that somatic Pol ε proofreading domain mutations occur in multiple sporadic tumours, where they underlie a phenotype of 'ultramutation' and favourable prognosis. In this Review, we summarize the current understanding of the mechanisms and consequences of polymerase proofreading domain mutations in human malignancies, and highlight the potential utility of these variants as novel cancer biomarkers and therapeutic targets. |
| spellingShingle | Rayner, E Van Gool, I Palles, C Kearsey, S Bosse, T Tomlinson, I Church, D A panoply of errors: polymerase proofreading domain mutations in cancer |
| title | A panoply of errors: polymerase proofreading domain mutations in cancer |
| title_full | A panoply of errors: polymerase proofreading domain mutations in cancer |
| title_fullStr | A panoply of errors: polymerase proofreading domain mutations in cancer |
| title_full_unstemmed | A panoply of errors: polymerase proofreading domain mutations in cancer |
| title_short | A panoply of errors: polymerase proofreading domain mutations in cancer |
| title_sort | panoply of errors polymerase proofreading domain mutations in cancer |
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