Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment

The cellular genome is constantly subject to DNA damage caused by endogenous factors or exogenously by damaging agents such as ionizing radiation or various anticancer agents. The base excision repair (BER) enzyme, DNA polymerase β, and the polymerases involved in translesion synthesis (TLS) have be...

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Main Authors: Nicolay, N, Helleday, T, Sharma, R
Format: Journal article
Language:English
Published: 2012
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author Nicolay, N
Helleday, T
Sharma, R
author_facet Nicolay, N
Helleday, T
Sharma, R
author_sort Nicolay, N
collection OXFORD
description The cellular genome is constantly subject to DNA damage caused by endogenous factors or exogenously by damaging agents such as ionizing radiation or various anticancer agents. The base excision repair (BER) enzyme, DNA polymerase β, and the polymerases involved in translesion synthesis (TLS) have been shown to contribute to cellular tolerance and repair of DNA lesions by anticancer treatments, particularly the platinum cytotoxic drugs. Moreover, there is robust preclinical evidence linking alterations in DNA pol β and TLS polymerase levels to cancer. DNA polymerases may therefore be potential targets to increase the sensitivity of cancer cells to chemotherapy drugs. In this article, the physical and chemical properties of DNA polymerase β and the translesion synthesis polymerases are reviewed with a view to identifying how they may act as targets for anticancer treatment. The potential clinical role of new DNA polymerase inhibitors is discussed and how they may be combined with conventional cytotoxic agents. © 2012 Bentham Science Publishers.
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spelling oxford-uuid:9f376845-ccfe-460c-8048-61b51e5986d92022-03-27T00:55:50ZBiological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9f376845-ccfe-460c-8048-61b51e5986d9EnglishSymplectic Elements at Oxford2012Nicolay, NHelleday, TSharma, RThe cellular genome is constantly subject to DNA damage caused by endogenous factors or exogenously by damaging agents such as ionizing radiation or various anticancer agents. The base excision repair (BER) enzyme, DNA polymerase β, and the polymerases involved in translesion synthesis (TLS) have been shown to contribute to cellular tolerance and repair of DNA lesions by anticancer treatments, particularly the platinum cytotoxic drugs. Moreover, there is robust preclinical evidence linking alterations in DNA pol β and TLS polymerase levels to cancer. DNA polymerases may therefore be potential targets to increase the sensitivity of cancer cells to chemotherapy drugs. In this article, the physical and chemical properties of DNA polymerase β and the translesion synthesis polymerases are reviewed with a view to identifying how they may act as targets for anticancer treatment. The potential clinical role of new DNA polymerase inhibitors is discussed and how they may be combined with conventional cytotoxic agents. © 2012 Bentham Science Publishers.
spellingShingle Nicolay, N
Helleday, T
Sharma, R
Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment
title Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment
title_full Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment
title_fullStr Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment
title_full_unstemmed Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment
title_short Biological relevance of DNA polymerase beta and translesion synthesis polymerases to cancer and its treatment
title_sort biological relevance of dna polymerase beta and translesion synthesis polymerases to cancer and its treatment
work_keys_str_mv AT nicolayn biologicalrelevanceofdnapolymerasebetaandtranslesionsynthesispolymerasestocanceranditstreatment
AT helledayt biologicalrelevanceofdnapolymerasebetaandtranslesionsynthesispolymerasestocanceranditstreatment
AT sharmar biologicalrelevanceofdnapolymerasebetaandtranslesionsynthesispolymerasestocanceranditstreatment