Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy

dc.contributor.authorNickoloff, Jac A.
dc.contributor.authorSharma, Neelam
dc.contributor.authorTaylor, Lynn
dc.contributor.authorAllen, Sage J.
dc.contributor.authorLee, Suk-Hee
dc.contributor.authorHromas, Robert
dc.contributor.departmentBiochemistry and Molecular Biology, School of Medicine
dc.date.accessioned2023-05-15T10:32:00Z
dc.date.available2023-05-15T10:32:00Z
dc.date.issued2022-01-28
dc.description.abstractCells 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationNickoloff JA, Sharma N, Taylor L, Allen SJ, Lee SH, Hromas R. Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy. Front Oncol. 2022;12:808757. Published 2022 Jan 28. doi:10.3389/fonc.2022.808757en_US
dc.identifier.urihttps://hdl.handle.net/1805/32952
dc.language.isoen_USen_US
dc.publisherFrontiers Mediaen_US
dc.relation.isversionof10.3389/fonc.2022.808757en_US
dc.relation.journalFrontiers in Oncologyen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePMCen_US
dc.subjectDNA repairen_US
dc.subjectDNA double-strand breaksen_US
dc.subjectGenome instabilityen_US
dc.subjectHomologous recombinationen_US
dc.subjectNon-homologous end-joiningen_US
dc.subjectChromosome decatenationen_US
dc.subjectDNA damageen_US
dc.titleMetnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapyen_US
dc.typeArticleen_US
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