1. Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets
- Author
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Chandini Bhaskar Naidu, Joanna Timmins, Fabienne Hans, Muge Senarisoy, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
- Subjects
DNA Repair ,Review ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,MESH: Structure-Activity Relationship ,Neoplasms ,MESH: Molecular Targeted Therapy ,inhibitors ,MESH: Animals ,MESH: Neoplasms ,Molecular Targeted Therapy ,MESH: DNA Glycosylases ,lcsh:QH301-705.5 ,Spectroscopy ,chemistry.chemical_classification ,MESH: DNA Repair ,0303 health sciences ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,MESH: Gene Expression Regulation, Enzymologic ,General Medicine ,Base excision repair ,3. Good health ,Computer Science Applications ,DNA glycosylases ,030220 oncology & carcinogenesis ,Disease Susceptibility ,MESH: Enzyme Activation ,DNA repair ,MESH: Disease Susceptibility ,Antineoplastic Agents ,Biology ,base excision repair ,Catalysis ,Gene Expression Regulation, Enzymologic ,Inorganic Chemistry ,03 medical and health sciences ,Structure-Activity Relationship ,medicine ,Animals ,Humans ,cancer ,Physical and Theoretical Chemistry ,Molecular Biology ,030304 developmental biology ,MESH: DNA Damage ,MESH: Humans ,drug resistance ,Mechanism (biology) ,Organic Chemistry ,Cancer ,medicine.disease ,Enzyme Activation ,Enzyme ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,DNA glycosylase ,Cancer cell ,Cancer research ,MESH: Antineoplastic Agents ,DNA ,DNA Damage - Abstract
International audience; 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.
- Published
- 2020