Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks.
DNA damage
Double-strand break (DSB)
MRX/MRN
Mre11
Rad50
Xrs2/NBS1
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2020
2020
Historique:
received:
22
03
2020
revised:
07
05
2020
accepted:
09
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
4
6
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32489527
doi: 10.1016/j.csbj.2020.05.013
pii: S2001-0370(20)30276-2
pmc: PMC7260605
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1137-1152Informations de copyright
© 2020 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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