Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks
Chromosomal DNA double-strand breaks (DSBs) are potentially lethal DNA lesions that pose a significant threat to genome stability and therefore need to be repaired to preserve genome integrity. Eukaryotic cells possess two main mechanisms for repairing DSBs: non-homologous end-joining (NHEJ) and hom...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037020302762 |
| _version_ | 1818665556773961728 |
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| author | Renata Tisi Jacopo Vertemara Giuseppe Zampella Maria Pia Longhese |
| author_facet | Renata Tisi Jacopo Vertemara Giuseppe Zampella Maria Pia Longhese |
| author_sort | Renata Tisi |
| collection | DOAJ |
| description | Chromosomal DNA double-strand breaks (DSBs) are potentially lethal DNA lesions that pose a significant threat to genome stability and therefore need to be repaired to preserve genome integrity. Eukaryotic cells possess two main mechanisms for repairing DSBs: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR requires that the 5′ terminated strands at both DNA ends are nucleolytically degraded by a concerted action of nucleases in a process termed DNA-end resection. This degradation leads to the formation of 3′-ended single-stranded DNA (ssDNA) ends that are essential to use homologous DNA sequences for repair. The evolutionarily conserved Mre11-Rad50-Xrs2/NBS1 complex (MRX/MRN) has enzymatic and structural activities to initiate DSB resection and to maintain the DSB ends tethered to each other for their repair. Furthermore, it is required to recruit and activate the protein kinase Tel1/ATM, which plays a key role in DSB signaling. All these functions depend on ATP-regulated DNA binding and nucleolytic activities of the complex. Several structures have been obtained in recent years for Mre11 and Rad50 subunits from archaea, and a few from the bacterial and eukaryotic orthologs. Nevertheless, the mechanism of activation of this protein complex is yet to be fully elucidated. In this review, we focused on recent biophysical and structural insights on the MRX complex and their interplay. |
| first_indexed | 2024-12-17T05:50:31Z |
| format | Article |
| id | doaj.art-4dedffd3a5d7458d84af120937dca517 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-12-17T05:50:31Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-4dedffd3a5d7458d84af120937dca5172022-12-21T22:01:10ZengElsevierComputational and Structural Biotechnology Journal2001-03702020-01-011811371152Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaksRenata Tisi0Jacopo Vertemara1Giuseppe Zampella2Maria Pia Longhese3Corresponding authors.; Dipartimento di Biotecnologie and Bioscienze, Università degli Studi di Milano-Bicocca, Milan, ItalyDipartimento di Biotecnologie and Bioscienze, Università degli Studi di Milano-Bicocca, Milan, ItalyDipartimento di Biotecnologie and Bioscienze, Università degli Studi di Milano-Bicocca, Milan, ItalyCorresponding authors.; Dipartimento di Biotecnologie and Bioscienze, Università degli Studi di Milano-Bicocca, Milan, ItalyChromosomal DNA double-strand breaks (DSBs) are potentially lethal DNA lesions that pose a significant threat to genome stability and therefore need to be repaired to preserve genome integrity. Eukaryotic cells possess two main mechanisms for repairing DSBs: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR requires that the 5′ terminated strands at both DNA ends are nucleolytically degraded by a concerted action of nucleases in a process termed DNA-end resection. This degradation leads to the formation of 3′-ended single-stranded DNA (ssDNA) ends that are essential to use homologous DNA sequences for repair. The evolutionarily conserved Mre11-Rad50-Xrs2/NBS1 complex (MRX/MRN) has enzymatic and structural activities to initiate DSB resection and to maintain the DSB ends tethered to each other for their repair. Furthermore, it is required to recruit and activate the protein kinase Tel1/ATM, which plays a key role in DSB signaling. All these functions depend on ATP-regulated DNA binding and nucleolytic activities of the complex. Several structures have been obtained in recent years for Mre11 and Rad50 subunits from archaea, and a few from the bacterial and eukaryotic orthologs. Nevertheless, the mechanism of activation of this protein complex is yet to be fully elucidated. In this review, we focused on recent biophysical and structural insights on the MRX complex and their interplay.http://www.sciencedirect.com/science/article/pii/S2001037020302762Double-strand break (DSB)DNA damageMRX/MRNMre11Rad50Xrs2/NBS1 |
| spellingShingle | Renata Tisi Jacopo Vertemara Giuseppe Zampella Maria Pia Longhese Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks Computational and Structural Biotechnology Journal Double-strand break (DSB) DNA damage MRX/MRN Mre11 Rad50 Xrs2/NBS1 |
| title | Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks |
| title_full | Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks |
| title_fullStr | Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks |
| title_full_unstemmed | Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks |
| title_short | Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks |
| title_sort | functional and structural insights into the mrx mrn complex a key player in recognition and repair of dna double strand breaks |
| topic | Double-strand break (DSB) DNA damage MRX/MRN Mre11 Rad50 Xrs2/NBS1 |
| url | http://www.sciencedirect.com/science/article/pii/S2001037020302762 |
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