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dc.contributor.authorFang, Minggang
dc.contributor.authorXia, Fen
dc.contributor.authorMahalingam, Meera
dc.contributor.authorVirbasius, Ching-Man A.
dc.contributor.authorWajapeyee, Narendra
dc.contributor.authorGreen, Michael R.
dc.date2022-08-11T08:08:29.000
dc.date.accessioned2022-08-23T15:56:52Z
dc.date.available2022-08-23T15:56:52Z
dc.date.issued2013-07-01
dc.date.submitted2013-06-05
dc.identifier.citationMol Cell Biol. 2013 Jul;33(13):2635-47. doi: 10.1128/MCB.00167-13. <a href="http://dx.doi.org/10.1128/MCB.00167-13">Link to article on publisher's site</a>
dc.identifier.issn0270-7306 (Linking)
dc.identifier.doi10.1128/MCB.00167-13
dc.identifier.pmid23648481
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30066
dc.description.abstractMultiple endocrine neoplasia type 1 is a familial cancer syndrome resulting from loss-of-function mutations in the MEN1 gene. We previously identified the tumor suppressor MEN1 as a gene required for oncogene-induced senescence in melanocytes, raising the possibility that MEN1 is a melanoma tumor suppressor. Here we show that MEN1 expression is lost in a high percentage of human melanomas and melanoma cell lines. We find that melanocytes depleted of MEN1 are deficient in homologous recombination (HR)-directed DNA repair, which is accompanied by increased non-homologous end joining activity. Following DNA damage, MEN1 levels increase resulting from phosphorylation by the DNA damage kinase ATM/ATR. Most importantly, we show that MEN1 functions by directly stimulating transcription of several genes, including BRCA1, RAD51 and RAD51AP1, that encode proteins involved in HR. MEN1 and its coactivator, the histone methyltransferase MLL, are recruited to the BRCA1, RAD51 and RAD51AP1 promoters by estrogen receptor 1, resulting in increased histone H3-lysine 4 trimethylation and transcription. Collectively, our results indicate that MEN1 is a melanoma tumor suppressor that functions by stimulating transcription of genes involved in HR-directed DNA repair.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23648481&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1128/MCB.00167-13
dc.subjectMultiple Endocrine Neoplasia Type 1
dc.subjectGenes, Tumor Suppressor
dc.subjectRecombinational DNA Repair
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectCancer Biology
dc.subjectGenetics and Genomics
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.titleMEN1 is a Melanoma Tumor Suppressor that Preserves Genomic Integrity by Stimulating Transcription of Genes that Promote Homologous Recombination-Directed DNA Repair
dc.typeJournal Article
dc.source.journaltitleMolecular and cellular biology
dc.source.volume33
dc.source.issue13
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/30
dc.identifier.contextkey4199960
html.description.abstract<p>Multiple endocrine neoplasia type 1 is a familial cancer syndrome resulting from loss-of-function mutations in the MEN1 gene. We previously identified the tumor suppressor MEN1 as a gene required for oncogene-induced senescence in melanocytes, raising the possibility that MEN1 is a melanoma tumor suppressor. Here we show that MEN1 expression is lost in a high percentage of human melanomas and melanoma cell lines. We find that melanocytes depleted of MEN1 are deficient in homologous recombination (HR)-directed DNA repair, which is accompanied by increased non-homologous end joining activity. Following DNA damage, MEN1 levels increase resulting from phosphorylation by the DNA damage kinase ATM/ATR. Most importantly, we show that MEN1 functions by directly stimulating transcription of several genes, including BRCA1, RAD51 and RAD51AP1, that encode proteins involved in HR. MEN1 and its coactivator, the histone methyltransferase MLL, are recruited to the BRCA1, RAD51 and RAD51AP1 promoters by estrogen receptor 1, resulting in increased histone H3-lysine 4 trimethylation and transcription. Collectively, our results indicate that MEN1 is a melanoma tumor suppressor that functions by stimulating transcription of genes involved in HR-directed DNA repair.</p>
dc.identifier.submissionpathfaculty_pubs/30
dc.contributor.departmentProgram in Gene Function and Expression
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages2635-47


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