Inhibition of MRN activity by a telomere protein motif

The MRN complex (MRX in Saccharomyces cerevisiae , made of Mre11, Rad50 and Nbs1/Xrs2) initiates double-stranded DNA break repair and activates the Tel1/ATM kinase in the DNA damage response. Telomeres counter both outcomes at chromosome ends, partly by keeping MRN-ATM in check. We show that MRX is...

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Bibliographic Details
Published in:Nature communications 2021-06, Vol.12 (1), p.3856-3856, Article 3856
Main Authors: Khayat, Freddy, Cannavo, Elda, Alshmery, Majedh, Foster, William R., Chahwan, Charly, Maddalena, Martino, Smith, Christopher, Oliver, Antony W., Watson, Adam T., Carr, Antony M., Cejka, Petr, Bianchi, Alessandro
Format: Article
Language:English
Subjects:
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Chromosomes
Damage
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Endonuclease
Eukaryotes
Homology
Humanities and Social Sciences
Kinases
MRE11 protein
multidisciplinary
N-Terminus
Non-homologous end joining
Origin recognition complex
Proteins
Repair
Science
Science (multidisciplinary)
Telomeres
Tethering
Yeast
Yeasts
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Summary:The MRN complex (MRX in Saccharomyces cerevisiae , made of Mre11, Rad50 and Nbs1/Xrs2) initiates double-stranded DNA break repair and activates the Tel1/ATM kinase in the DNA damage response. Telomeres counter both outcomes at chromosome ends, partly by keeping MRN-ATM in check. We show that MRX is disabled by telomeric protein Rif2 through an N-terminal motif (MIN, M RN/X- in hibitory motif). MIN executes suppression of Tel1, DNA end-resection and non-homologous end joining by binding the Rad50 N-terminal region. Our data suggest that MIN promotes a transition within MRX that is not conductive for endonuclease activity, DNA-end tethering or Tel1 kinase activation, highlighting an Achilles’ heel in MRN, which we propose is also exploited by the RIF2 paralog ORC4 (Origin Recognition Complex 4) in Kluyveromyces lactis and the Schizosaccharomyces pombe telomeric factor Taz1, which is evolutionarily unrelated to Orc4/Rif2. This raises the possibility that analogous mechanisms might be deployed in other eukaryotes as well. Telomeres suppress the DNA damage response at chromosome ends. Here the authors show that in budding yeast the activity of the MRX complex in DNA repair and DNA damage signaling is inhibited by telomeric protein Rif2 via a short motif at the N-terminus.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24047-2