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.
Tisi, R., Vertemara, J., Zampella, G., & Longhese, M. (2020). 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, 18, 1137-1152.
|Citazione:||Tisi, R., Vertemara, J., Zampella, G., & Longhese, M. (2020). 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, 18, 1137-1152.|
|Tipo:||Articolo in rivista - Review Essay|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||Functional and structural insights into the MRX/MRN complex, a key player in recognition and repair of DNA double-strand breaks|
|Autori:||Tisi, R; Vertemara, J; Zampella, G; Longhese, M|
TISI, RENATA ANITA (Co-primo) (Corresponding)
VERTEMARA, JACOPO (Co-primo)
ZAMPELLA, GIUSEPPE (Penultimo)
LONGHESE, MARIA PIA (Ultimo) (Corresponding)
|Data di pubblicazione:||2020|
|Rivista:||COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.csbj.2020.05.013|
|Appare nelle tipologie:||01 - Articolo su rivista|