Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets
Cancer is the second leading cause of death with tens of millions of people diagnosed with cancer every year around the world. Most radio- and chemotherapies aim to eliminate cancer cells, notably by causing severe damage to the DNA. However, efficient repair of such damage represents a common mecha...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9226 |
| _version_ | 1797545832422047744 |
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| author | Fabienne Hans Muge Senarisoy Chandini Bhaskar Naidu Joanna Timmins |
| author_facet | Fabienne Hans Muge Senarisoy Chandini Bhaskar Naidu Joanna Timmins |
| author_sort | Fabienne Hans |
| collection | DOAJ |
| description | Cancer is the second leading cause of death with tens of millions of people diagnosed with cancer every year around the world. Most radio- and chemotherapies aim to eliminate cancer cells, notably by causing severe damage to the DNA. However, efficient repair of such damage represents a common mechanism of resistance to initially effective cytotoxic agents. Thus, development of new generation anticancer drugs that target DNA repair pathways, and more particularly the base excision repair (BER) pathway that is responsible for removal of damaged bases, is of growing interest. The BER pathway is initiated by a set of enzymes known as DNA glycosylases. Unlike several downstream BER enzymes, DNA glycosylases have so far received little attention and the development of specific inhibitors of these enzymes has been lagging. Yet, dysregulation of DNA glycosylases is also known to play a central role in numerous cancers and at different stages of the disease, and thus inhibiting DNA glycosylases is now considered a valid strategy to eliminate cancer cells. This review provides a detailed overview of the activities of DNA glycosylases in normal and cancer cells, their modes of regulation, and their potential as anticancer drug targets. |
| first_indexed | 2024-03-10T14:20:39Z |
| format | Article |
| id | doaj.art-a4fbfc9cec1546e0bcb66c50322336c8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:20:39Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a4fbfc9cec1546e0bcb66c50322336c82023-11-20T23:23:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012123922610.3390/ijms21239226Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug TargetsFabienne Hans0Muge Senarisoy1Chandini Bhaskar Naidu2Joanna Timmins3Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, F-38000 Grenoble, FranceInstitut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, F-38000 Grenoble, FranceInstitut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, F-38000 Grenoble, FranceInstitut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, F-38000 Grenoble, FranceCancer is the second leading cause of death with tens of millions of people diagnosed with cancer every year around the world. Most radio- and chemotherapies aim to eliminate cancer cells, notably by causing severe damage to the DNA. However, efficient repair of such damage represents a common mechanism of resistance to initially effective cytotoxic agents. Thus, development of new generation anticancer drugs that target DNA repair pathways, and more particularly the base excision repair (BER) pathway that is responsible for removal of damaged bases, is of growing interest. The BER pathway is initiated by a set of enzymes known as DNA glycosylases. Unlike several downstream BER enzymes, DNA glycosylases have so far received little attention and the development of specific inhibitors of these enzymes has been lagging. Yet, dysregulation of DNA glycosylases is also known to play a central role in numerous cancers and at different stages of the disease, and thus inhibiting DNA glycosylases is now considered a valid strategy to eliminate cancer cells. This review provides a detailed overview of the activities of DNA glycosylases in normal and cancer cells, their modes of regulation, and their potential as anticancer drug targets.https://www.mdpi.com/1422-0067/21/23/9226cancerbase excision repairDNA glycosylasesdrug resistanceinhibitors |
| spellingShingle | Fabienne Hans Muge Senarisoy Chandini Bhaskar Naidu Joanna Timmins Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets International Journal of Molecular Sciences cancer base excision repair DNA glycosylases drug resistance inhibitors |
| title | Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets |
| title_full | Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets |
| title_fullStr | Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets |
| title_full_unstemmed | Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets |
| title_short | Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets |
| title_sort | focus on dna glycosylases a set of tightly regulated enzymes with a high potential as anticancer drug targets |
| topic | cancer base excision repair DNA glycosylases drug resistance inhibitors |
| url | https://www.mdpi.com/1422-0067/21/23/9226 |
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