Biomolecules | |
ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor | |
Martin F. Lavin1  Sergei Kozlov2  Magtouf Gatei2  Amanda W. Kijas2  Wolf-Dietrich Heyer2  Thomas Helleday2  | |
[1] UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia; | |
关键词: DNA double strand breaks; oxidative stress; ATM activation; Mre11/Rad50/Nbs1 complex; phosphorylation; adaptor role; | |
DOI : 10.3390/biom5042877 | |
来源: mdpi | |
【 摘 要 】
The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes.
【 授权许可】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
【 预 览 】
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RO202003190004520ZK.pdf | 2361KB | download |