The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair

SETMAR is a fusion between a SET-domain methyltransferase gene and a mariner-family transposase gene, which is specific to anthropoid primates. However, the ancestral SET gene is present in all other mammals and birds. SETMAR is reported to be involved in transcriptional regulation and a diverse set...

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Main Authors: Tellier, M, Chalmers, R
Format: Journal article
Language:English
Published: Elsevier 2019
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author Tellier, M
Chalmers, R
author_facet Tellier, M
Chalmers, R
author_sort Tellier, M
collection OXFORD
description SETMAR is a fusion between a SET-domain methyltransferase gene and a mariner-family transposase gene, which is specific to anthropoid primates. However, the ancestral SET gene is present in all other mammals and birds. SETMAR is reported to be involved in transcriptional regulation and a diverse set of reactions related to DNA repair. Since the transcriptional effects of SETMAR depend on site-specific DNA binding, and are perturbed by inactivating the methyltransferase, we wondered whether we could differentiate the effects of the SET and MAR domains in DNA repair assays. We therefore generated several stable U2OS cell lines expressing either wild type SETMAR or truncation or point mutant variants. We tested these cell lines with in vivo plasmid-based assays to determine the relevance of the different domains and activities of SETMAR in DNA repair. Contrary to previous reports, we found that wild type SETMAR had little to no effect on the rate of cell division, DNA integration into the genome or non-homologous end joining. Also contrary to previous reports, we failed to detect any effect of a strong active-site mutation that should have knocked out the putative nuclease activity of SETMAR.
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spelling oxford-uuid:f35b154d-bdb3-4f7f-8537-b82c47af5ef02022-03-27T12:11:31ZThe roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repairJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f35b154d-bdb3-4f7f-8537-b82c47af5ef0EnglishSymplectic Elements at OxfordElsevier2019Tellier, MChalmers, RSETMAR is a fusion between a SET-domain methyltransferase gene and a mariner-family transposase gene, which is specific to anthropoid primates. However, the ancestral SET gene is present in all other mammals and birds. SETMAR is reported to be involved in transcriptional regulation and a diverse set of reactions related to DNA repair. Since the transcriptional effects of SETMAR depend on site-specific DNA binding, and are perturbed by inactivating the methyltransferase, we wondered whether we could differentiate the effects of the SET and MAR domains in DNA repair assays. We therefore generated several stable U2OS cell lines expressing either wild type SETMAR or truncation or point mutant variants. We tested these cell lines with in vivo plasmid-based assays to determine the relevance of the different domains and activities of SETMAR in DNA repair. Contrary to previous reports, we found that wild type SETMAR had little to no effect on the rate of cell division, DNA integration into the genome or non-homologous end joining. Also contrary to previous reports, we failed to detect any effect of a strong active-site mutation that should have knocked out the putative nuclease activity of SETMAR.
spellingShingle Tellier, M
Chalmers, R
The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair
title The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair
title_full The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair
title_fullStr The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair
title_full_unstemmed The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair
title_short The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair
title_sort roles of the human setmar metnase protein in illegitimate dna recombination and non homologous end joining repair
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