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XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia

Overview of attention for article published in Nature, December 2016
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (61st percentile)

Citations

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213 Dimensions

Readers on

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333 Mendeley
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2 CiteULike
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Title
XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia
Published in
Nature, December 2016
DOI 10.1038/nature20790
Pubmed ID
Authors

Nicolas C. Hoch, Hana Hanzlikova, Stuart L. Rulten, Martine Tétreault, Emilia Komulainen, Limei Ju, Peter Hornyak, Zhihong Zeng, William Gittens, Stephanie A. Rey, Kevin Staras, Grazia M. S. Mancini, Peter J. McKinnon, Zhao-Qi Wang, Justin D. Wagner, Grace Yoon, Keith W. Caldecott

Abstract

XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. This latter phenotype is recapitulated in a related syndrome caused by mutations in the XRCC1 partner protein PNKP and implicates hyperactivation of poly(ADP-ribose) polymerase/s as a cause of cerebellar ataxia. Indeed, remarkably, genetic deletion of Parp1 rescued normal cerebellar ADP-ribose levels and reduced the loss of cerebellar neurons and ataxia in Xrcc1-defective mice, identifying a molecular mechanism by which endogenous single-strand breaks trigger neuropathology. Collectively, these data establish the importance of XRCC1 protein complexes for normal neurological function and identify PARP1 as a therapeutic target in DNA strand break repair-defective disease.

X Demographics

X Demographics

The data shown below were collected from the profiles of 70 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 333 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Switzerland 1 <1%
Italy 1 <1%
United Kingdom 1 <1%
Japan 1 <1%
United States 1 <1%
Poland 1 <1%
Unknown 327 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 69 21%
Researcher 47 14%
Student > Master 34 10%
Student > Bachelor 34 10%
Student > Doctoral Student 17 5%
Other 60 18%
Unknown 72 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 111 33%
Agricultural and Biological Sciences 59 18%
Medicine and Dentistry 30 9%
Neuroscience 24 7%
Chemistry 7 2%
Other 27 8%
Unknown 75 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 122. 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 29 June 2018.
All research outputs
#336,315
of 25,070,356 outputs
Outputs from Nature
#17,665
of 96,665 outputs
Outputs of similar age
#7,171
of 432,528 outputs
Outputs of similar age from Nature
#338
of 886 outputs
Altmetric has tracked 25,070,356 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 96,665 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.3. This one has done well, scoring higher than 81% of its peers.
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 432,528 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 886 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.