SETMAR

SETMAR contains a SET domain that confers its histone methyltransferase activity, on Lys-4 and Lys-36 of Histone H3, both of which are specific tags for epigenetic activation. It has been identified as a repair protein as it mediates dimethylation at Lys-36 at double-strand break locations, a signal enhancing NHEJ repair.{{cite journal | vauthors = Lee SH, Oshige M, Durant ST, Rasila KK, Williamson EA, Ramsey H, Kwan L, Nickoloff JA, Hromas R | display-authors = 6 | title = The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 50 | pages = 18075–18080 | date = December 2005 | pmid = 16332963 | pmc = 1312370 | doi = 10.1073/pnas.0503676102 | doi-access = free | bibcode = 2005PNAS..10218075L }}{{cite journal | vauthors = Fnu S, Williamson EA, De Haro LP, Brenneman M, Wray J, Shaheen M, Radhakrishnan K, Lee SH, Nickoloff JA, Hromas R | display-authors = 6 | title = Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 2 | pages = 540–545 | date = January 2011 | pmid = 21187428 | pmc = 3021059 | doi = 10.1073/pnas.1013571108 | doi-access = free | bibcode = 2011PNAS..108..540F }}

Anthropoid primates, including humans, have a version of the protein fused to a Mariner/Tc1 transposase. This fusion region provides the DNA-binding abilities for the protein as well as some nuclease activity. The transposase activity is lost due to the presence of several inactivating mutations,{{cite journal | vauthors = Tellier M, Chalmers R | title = Compensating for over-production inhibition of the Hsmar1 transposon in Escherichia coli using a series of constitutive promoters | journal = Mobile DNA | volume = 11 | issue = 1 | pages = 5 | date = 2020-01-10 | pmid = 31938044 | pmc = 6954556 | doi = 10.1186/s13100-020-0200-5 | doi-access = free }} including the D610N mutation.{{cite journal | vauthors = Miskey C, Papp B, Mátés L, Sinzelle L, Keller H, Izsvák Z, Ivics Z | title = The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends | journal = Molecular and Cellular Biology | volume = 27 | issue = 12 | pages = 4589–4600 | date = June 2007 | pmid = 17403897 | pmc = 1900042 | doi = 10.1128/MCB.02027-06 }}{{cite journal | vauthors = Liu D, Bischerour J, Siddique A, Buisine N, Bigot Y, Chalmers R | title = The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase | journal = Molecular and Cellular Biology | volume = 27 | issue = 3 | pages = 1125–1132 | date = February 2007 | pmid = 17130240 | pmc = 1800679 | doi = 10.1128/MCB.01899-06 }} However, the domesticated transposase domain retains its ability to bind to the mariner repeat elements in the genome.{{cite journal | vauthors = Tellier M, Chalmers R | title = Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome | journal = Nucleic Acids Research | volume = 47 | issue = 1 | pages = 122–133 | date = January 2019 | pmid = 30329085 | doi = 10.1093/nar/gky937 | pmc = 6326780 }}{{cite journal | vauthors = Antoine-Lorquin A, Arensburger P, Arnaoty A, Asgari S, Batailler M, Beauclair L, Belleannée C, Buisine N, Coustham V, Guyetant S, Helou L, Lecomte T, Pitard B, Stévant I, Bigot Y | display-authors = 6 | title = Two repeated motifs enriched within some enhancers and origins of replication are bound by SETMAR isoforms in human colon cells | journal = Genomics | volume = 113 | issue = 3 | pages = 1589–1604 | date = May 2021 | pmid = 33812898 | doi = 10.1016/j.ygeno.2021.03.032 | s2cid = 233028866 | doi-access = free }}{{cite journal | vauthors = Miskei M, Horváth A, Viola L, Varga L, Nagy É, Feró O, Karányi Z, Roszik J, Miskey C, Ivics Z, Székvölgyi L | display-authors = 6 | title = Genome-wide mapping of binding sites of the transposase-derived SETMAR protein in the human genome | journal = Computational and Structural Biotechnology Journal | volume = 19 | pages = 4032–4041 | date = 2021-01-01 | pmid = 34377368 | pmc = 8327481 | doi = 10.1016/j.csbj.2021.07.010 }}{{cite journal | vauthors = Chen Q, Bates AM, Hanquier JN, Simpson E, Rusch DB, Podicheti R, Liu Y, Wek RC, Cornett EM, Georgiadis MM | display-authors = 6 | title = Structural and genome-wide analyses suggest that transposon-derived protein SETMAR alters transcription and splicing | language = English | journal = The Journal of Biological Chemistry | volume = 298 | issue = 5 | pages = 101894 | date = May 2022 | pmid = 35378129 | pmc = 9062482 | doi = 10.1016/j.jbc.2022.101894 | doi-access = free }} SETMAR has been found to affect the expression and splicing of genes close to or containing mariner repeat elements via its functions in histone methylation. Both the SET, via its methyltransferase activity,{{cite journal | vauthors = Tellier M, Chalmers R | title = The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair | journal = DNA Repair | volume = 80 | pages = 26–35 | date = August 2019 | pmid = 31238295 | pmc = 6715855 | doi = 10.1016/j.dnarep.2019.06.006 }} and the mariner, with its DNA-binding {{cite journal | vauthors = Beck BD, Park SJ, Lee YJ, Roman Y, Hromas RA, Lee SH | title = Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair | language = English | journal = The Journal of Biological Chemistry | volume = 283 | issue = 14 | pages = 9023–9030 | date = April 2008 | pmid = 18263876 | pmc = 2431028 | doi = 10.1074/jbc.M800150200 | doi-access = free }} and nuclease activities,{{cite journal | vauthors = Hromas R, Wray J, Lee SH, Martinez L, Farrington J, Corwin LK, Ramsey H, Nickoloff JA, Williamson EA | display-authors = 6 | title = The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining | journal = DNA Repair | volume = 7 | issue = 12 | pages = 1927–1937 | date = December 2008 | pmid = 18773976 | pmc = 2644637 | doi = 10.1016/j.dnarep.2008.08.002 }}{{cite journal | vauthors = Beck BD, Lee SS, Williamson E, Hromas RA, Lee SH | title = Biochemical characterization of metnase's endonuclease activity and its role in NHEJ repair | journal = Biochemistry | volume = 50 | issue = 20 | pages = 4360–4370 | date = May 2011 | pmid = 21491884 | pmc = 3388547 | doi = 10.1021/bi200333k }}{{cite journal | vauthors = Mohapatra S, Yannone SM, Lee SH, Hromas RA, Akopiants K, Menon V, Ramsden DA, Povirk LF | display-authors = 6 | title = Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases | journal = DNA Repair | volume = 12 | issue = 6 | pages = 422–432 | date = June 2013 | pmid = 23602515 | pmc = 3660496 | doi = 10.1016/j.dnarep.2013.03.005 }}{{cite journal | vauthors = Kim HS, Chen Q, Kim SK, Nickoloff JA, Hromas R, Georgiadis MM, Lee SH | title = The DDN catalytic motif is required for Metnase functions in non-homologous end joining (NHEJ) repair and replication restart | language = English | journal = The Journal of Biological Chemistry | volume = 289 | issue = 15 | pages = 10930–10938 | date = April 2014 | pmid = 24573677 | pmc = 4036204 | doi = 10.1074/jbc.M113.533216 | doi-access = free }} domains of SETMAR have been shown to act in non-homologous end joining (NHEJ) to repair DNA double strand breaks.

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Category:Genes mutated in mice