Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells
The MRN complex (MRE11, RAD50, NBS1/NBN) is a DNA double strand break sensor in eukaryotes. The complex directly participates in, or coordinates, several activities at the break such as DNA resection, activation of the DNA damage checkpoint, chromatin remodeling and recruitment of the repair machine...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/12/3794 |
| _version_ | 1797544560177446912 |
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| author | Matthew T. McPherson Ashton S. Holub Aman Y. Husbands Ruben C. Petreaca |
| author_facet | Matthew T. McPherson Ashton S. Holub Aman Y. Husbands Ruben C. Petreaca |
| author_sort | Matthew T. McPherson |
| collection | DOAJ |
| description | The MRN complex (MRE11, RAD50, NBS1/NBN) is a DNA double strand break sensor in eukaryotes. The complex directly participates in, or coordinates, several activities at the break such as DNA resection, activation of the DNA damage checkpoint, chromatin remodeling and recruitment of the repair machinery. Mutations in components of the MRN complex have been described in cancer cells for several decades. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) database, we characterized all the reported MRN mutations. This analysis revealed several hotspot frameshift mutations in all three genes that introduce premature stop codons and truncate large regions of the C-termini. We also found through evolutionary analyses that COSMIC mutations are enriched in conserved residues of NBS1/NBN and RAD50 but not in MRE11. Given that all three genes are important to carcinogenesis, we propose these differential enrichment patterns may reflect a more severe pleiotropic role for MRE11. |
| first_indexed | 2024-03-10T14:02:16Z |
| format | Article |
| id | doaj.art-a44ba77d90c945d4a10df81e4d06d1c2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:02:16Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a44ba77d90c945d4a10df81e4d06d1c22023-11-21T01:00:53ZengMDPI AGCancers2072-66942020-12-011212379410.3390/cancers12123794Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer CellsMatthew T. McPherson0Ashton S. Holub1Aman Y. Husbands2Ruben C. Petreaca3Department of Molecular Genetics, The Ohio State University, Columbus, OH 43215, USADepartment of Molecular Genetics, The Ohio State University, Columbus, OH 43215, USADepartment of Molecular Genetics, The Ohio State University, Columbus, OH 43215, USADepartment of Molecular Genetics, The Ohio State University, Columbus, OH 43215, USAThe MRN complex (MRE11, RAD50, NBS1/NBN) is a DNA double strand break sensor in eukaryotes. The complex directly participates in, or coordinates, several activities at the break such as DNA resection, activation of the DNA damage checkpoint, chromatin remodeling and recruitment of the repair machinery. Mutations in components of the MRN complex have been described in cancer cells for several decades. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) database, we characterized all the reported MRN mutations. This analysis revealed several hotspot frameshift mutations in all three genes that introduce premature stop codons and truncate large regions of the C-termini. We also found through evolutionary analyses that COSMIC mutations are enriched in conserved residues of NBS1/NBN and RAD50 but not in MRE11. Given that all three genes are important to carcinogenesis, we propose these differential enrichment patterns may reflect a more severe pleiotropic role for MRE11.https://www.mdpi.com/2072-6694/12/12/3794DNA double strand break (DSB)COSMICbreak sensorMRNgenetic recombination |
| spellingShingle | Matthew T. McPherson Ashton S. Holub Aman Y. Husbands Ruben C. Petreaca Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells Cancers DNA double strand break (DSB) COSMIC break sensor MRN genetic recombination |
| title | Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells |
| title_full | Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells |
| title_fullStr | Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells |
| title_full_unstemmed | Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells |
| title_short | Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells |
| title_sort | mutation spectra of the mrn mre11 rad50 nbs1 nbn break sensor in cancer cells |
| topic | DNA double strand break (DSB) COSMIC break sensor MRN genetic recombination |
| url | https://www.mdpi.com/2072-6694/12/12/3794 |
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