Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy
Cells respond to DNA damage by activating signaling and DNA repair systems, described as the DNA damage response (DDR). Clarifying DDR pathways and their dysregulation in cancer are important for understanding cancer etiology, how cancer cells exploit the DDR to survive endogenous and treatment-rela...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.808757/full |
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| author | Jac A. Nickoloff Neelam Sharma Lynn Taylor Sage J. Allen Suk-Hee Lee Robert Hromas |
| author_facet | Jac A. Nickoloff Neelam Sharma Lynn Taylor Sage J. Allen Suk-Hee Lee Robert Hromas |
| author_sort | Jac A. Nickoloff |
| collection | DOAJ |
| description | Cells respond to DNA damage by activating signaling and DNA repair systems, described as the DNA damage response (DDR). Clarifying DDR pathways and their dysregulation in cancer are important for understanding cancer etiology, how cancer cells exploit the DDR to survive endogenous and treatment-related stress, and to identify DDR targets as therapeutic targets. Cancer is often treated with genotoxic chemicals and/or ionizing radiation. These agents are cytotoxic because they induce DNA double-strand breaks (DSBs) directly, or indirectly by inducing replication stress which causes replication fork collapse to DSBs. EEPD1 and Metnase are structure-specific nucleases, and Metnase is also a protein methyl transferase that methylates histone H3 and itself. EEPD1 and Metnase promote repair of frank, two-ended DSBs, and both promote the timely and accurate restart of replication forks that have collapsed to single-ended DSBs. In addition to its roles in HR, Metnase also promotes DSB repair by classical non-homologous recombination, and chromosome decatenation mediated by TopoIIα. Although mutations in Metnase and EEPD1 are not common in cancer, both proteins are frequently overexpressed, which may help tumor cells manage oncogenic stress or confer resistance to therapeutics. Here we focus on Metnase and EEPD1 DNA repair pathways, and discuss opportunities for targeting these pathways to enhance cancer therapy. |
| first_indexed | 2024-12-13T13:38:51Z |
| format | Article |
| id | doaj.art-b605f433059f48d88d8cde52045475f5 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-13T13:38:51Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b605f433059f48d88d8cde52045475f52022-12-21T23:43:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011210.3389/fonc.2022.808757808757Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer TherapyJac A. Nickoloff0Neelam Sharma1Lynn Taylor2Sage J. Allen3Suk-Hee Lee4Robert Hromas5Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United StatesDivision of Hematology and Medical Oncology, Department of Medicine and the Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, United StatesCells respond to DNA damage by activating signaling and DNA repair systems, described as the DNA damage response (DDR). Clarifying DDR pathways and their dysregulation in cancer are important for understanding cancer etiology, how cancer cells exploit the DDR to survive endogenous and treatment-related stress, and to identify DDR targets as therapeutic targets. Cancer is often treated with genotoxic chemicals and/or ionizing radiation. These agents are cytotoxic because they induce DNA double-strand breaks (DSBs) directly, or indirectly by inducing replication stress which causes replication fork collapse to DSBs. EEPD1 and Metnase are structure-specific nucleases, and Metnase is also a protein methyl transferase that methylates histone H3 and itself. EEPD1 and Metnase promote repair of frank, two-ended DSBs, and both promote the timely and accurate restart of replication forks that have collapsed to single-ended DSBs. In addition to its roles in HR, Metnase also promotes DSB repair by classical non-homologous recombination, and chromosome decatenation mediated by TopoIIα. Although mutations in Metnase and EEPD1 are not common in cancer, both proteins are frequently overexpressed, which may help tumor cells manage oncogenic stress or confer resistance to therapeutics. Here we focus on Metnase and EEPD1 DNA repair pathways, and discuss opportunities for targeting these pathways to enhance cancer therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.808757/fullDNA repairDNA double-strand breaksgenome instabilityhomologous recombinationnon-homologous end-joiningchromosome decatenation |
| spellingShingle | Jac A. Nickoloff Neelam Sharma Lynn Taylor Sage J. Allen Suk-Hee Lee Robert Hromas Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy Frontiers in Oncology DNA repair DNA double-strand breaks genome instability homologous recombination non-homologous end-joining chromosome decatenation |
| title | Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy |
| title_full | Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy |
| title_fullStr | Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy |
| title_full_unstemmed | Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy |
| title_short | Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy |
| title_sort | metnase and eepd1 dna repair functions and potential targets in cancer therapy |
| topic | DNA repair DNA double-strand breaks genome instability homologous recombination non-homologous end-joining chromosome decatenation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.808757/full |
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