Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex
The <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5612 |
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| author | Barbora Otahalova Zuzana Volkova Jana Soukupova Petra Kleiblova Marketa Janatova Michal Vocka Libor Macurek Zdenek Kleibl |
| author_facet | Barbora Otahalova Zuzana Volkova Jana Soukupova Petra Kleiblova Marketa Janatova Michal Vocka Libor Macurek Zdenek Kleibl |
| author_sort | Barbora Otahalova |
| collection | DOAJ |
| description | The <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the <i>MRE11</i>, <i>RAD50</i> and <i>NBN</i> genes. |
| first_indexed | 2024-03-11T06:26:27Z |
| format | Article |
| id | doaj.art-cefde8d11c7647b791fac81491e13a37 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:27Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cefde8d11c7647b791fac81491e13a372023-11-17T11:36:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246561210.3390/ijms24065612Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN ComplexBarbora Otahalova0Zuzana Volkova1Jana Soukupova2Petra Kleiblova3Marketa Janatova4Michal Vocka5Libor Macurek6Zdenek Kleibl7Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicDepartment of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicLaboratory of Cancer Cell Biology, Institute of Molecular Genetics, Czech Academy of Sciences, 14220 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech RepublicThe <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the <i>MRE11</i>, <i>RAD50</i> and <i>NBN</i> genes.https://www.mdpi.com/1422-0067/24/6/5612NBNMRE11RAD50NBSATLDNBSLD |
| spellingShingle | Barbora Otahalova Zuzana Volkova Jana Soukupova Petra Kleiblova Marketa Janatova Michal Vocka Libor Macurek Zdenek Kleibl Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex International Journal of Molecular Sciences NBN MRE11 RAD50 NBS ATLD NBSLD |
| title | Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex |
| title_full | Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex |
| title_fullStr | Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex |
| title_full_unstemmed | Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex |
| title_short | Importance of Germline and Somatic Alterations in Human <i>MRE11</i>, <i>RAD50</i>, and <i>NBN</i> Genes Coding for MRN Complex |
| title_sort | importance of germline and somatic alterations in human i mre11 i i rad50 i and i nbn i genes coding for mrn complex |
| topic | NBN MRE11 RAD50 NBS ATLD NBSLD |
| url | https://www.mdpi.com/1422-0067/24/6/5612 |
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