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Replication fork stability confers chemoresistance in BRCA-deficient cells

Overview of attention for article published in Nature, July 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)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

Citations

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677 Dimensions

Readers on

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736 Mendeley
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1 CiteULike
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Title
Replication fork stability confers chemoresistance in BRCA-deficient cells
Published in
Nature, July 2016
DOI 10.1038/nature18325
Pubmed ID
Authors

Arnab Ray Chaudhuri, Elsa Callen, Xia Ding, Ewa Gogola, Alexandra A. Duarte, Ji-Eun Lee, Nancy Wong, Vanessa Lafarga, Jennifer A. Calvo, Nicholas J. Panzarino, Sam John, Amanda Day, Anna Vidal Crespo, Binghui Shen, Linda M. Starnes, Julian R. de Ruiter, Jeremy A. Daniel, Panagiotis A. Konstantinopoulos, David Cortez, Sharon B. Cantor, Oscar Fernandez-Capetillo, Kai Ge, Jos Jonkers, Sven Rottenberg, Shyam K. Sharan, André Nussenzweig

Abstract

Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.

X Demographics

X Demographics

The data shown below were collected from the profiles of 54 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 736 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 <1%
France 1 <1%
Sweden 1 <1%
India 1 <1%
United Kingdom 1 <1%
Canada 1 <1%
United States 1 <1%
Unknown 728 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 174 24%
Researcher 133 18%
Student > Master 65 9%
Student > Bachelor 56 8%
Student > Doctoral Student 30 4%
Other 120 16%
Unknown 158 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 305 41%
Agricultural and Biological Sciences 155 21%
Medicine and Dentistry 56 8%
Chemistry 11 1%
Pharmacology, Toxicology and Pharmaceutical Science 9 1%
Other 37 5%
Unknown 163 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 150. 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 16 August 2022.
All research outputs
#271,431
of 25,199,971 outputs
Outputs from Nature
#15,174
of 96,956 outputs
Outputs of similar age
#5,496
of 373,185 outputs
Outputs of similar age from Nature
#325
of 954 outputs
Altmetric has tracked 25,199,971 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 96,956 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.4. This one has done well, scoring higher than 84% 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 373,185 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 954 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 66% of its contemporaries.