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ATM-dependent phosphorylation of MRE11 controls extent of resection during homology directed repair by signalling through Exonuclease 1

Overview of attention for article published in Nucleic Acids Research, August 2015
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Title
ATM-dependent phosphorylation of MRE11 controls extent of resection during homology directed repair by signalling through Exonuclease 1
Published in
Nucleic Acids Research, August 2015
DOI 10.1093/nar/gkv754
Pubmed ID
Authors

Amanda W. Kijas, Yi Chieh Lim, Emma Bolderson, Karen Cerosaletti, Magtouf Gatei, Burkhard Jakob, Frank Tobias, Gisela Taucher-Scholz, Nuri Gueven, Greg Oakley, Patrick Concannon, Ernst Wolvetang, Kum Kum Khanna, Lisa Wiesmüller, Martin F. Lavin

Abstract

The MRE11/RAD50/NBS1 (MRN) complex plays a central role as a sensor of DNA double strand breaks (DSB) and is responsible for the efficient activation of ataxia-telangiectasia mutated (ATM) kinase. Once activated ATM in turn phosphorylates RAD50 and NBS1, important for cell cycle control, DNA repair and cell survival. We report here that MRE11 is also phosphorylated by ATM at S676 and S678 in response to agents that induce DNA DSB, is dependent on the presence of NBS1, and does not affect the association of members of the complex or ATM activation. A phosphosite mutant (MRE11S676AS678A) cell line showed decreased cell survival and increased chromosomal aberrations after radiation exposure indicating a defect in DNA repair. Use of GFP-based DNA repair reporter substrates in MRE11S676AS678A cells revealed a defect in homology directed repair (HDR) but single strand annealing was not affected. More detailed investigation revealed that MRE11S676AS678A cells resected DNA ends to a greater extent at sites undergoing HDR. Furthermore, while ATM-dependent phosphorylation of Kap1 and SMC1 was normal in MRE11S676AS678A cells, there was no phosphorylation of Exonuclease 1 consistent with the defect in HDR. These results describe a novel role for ATM-dependent phosphorylation of MRE11 in limiting the extent of resection mediated through Exonuclease 1.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 124 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Bulgaria 1 <1%
Unknown 123 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 38 31%
Researcher 21 17%
Student > Bachelor 9 7%
Student > Master 8 6%
Student > Doctoral Student 6 5%
Other 14 11%
Unknown 28 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 45 36%
Agricultural and Biological Sciences 33 27%
Medicine and Dentistry 5 4%
Engineering 2 2%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Other 8 6%
Unknown 29 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 January 2016.
All research outputs
#17,766,929
of 22,818,766 outputs
Outputs from Nucleic Acids Research
#23,390
of 26,315 outputs
Outputs of similar age
#177,430
of 263,982 outputs
Outputs of similar age from Nucleic Acids Research
#203
of 282 outputs
Altmetric has tracked 22,818,766 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 26,315 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,982 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 282 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.