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Poly(ADP-ribose) Polymerase 1, PARP1, modifies EZH2 and inhibits EZH2 histone methyltransferase activity after DNA damage

Overview of attention for article published in Oncotarget, January 2018
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  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

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2 X users
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1 patent

Citations

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36 Mendeley
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Title
Poly(ADP-ribose) Polymerase 1, PARP1, modifies EZH2 and inhibits EZH2 histone methyltransferase activity after DNA damage
Published in
Oncotarget, January 2018
DOI 10.18632/oncotarget.24291
Pubmed ID
Authors

Lisa B. Caruso, Kayla A. Martin, Elisabetta Lauretti, Michael Hulse, Micheal Siciliano, Lena N. Lupey-Green, Aaron Abraham, Tomasz Skorski, Italo Tempera

Abstract

The enzyme Poly(ADP-ribose) polymerase 1 (PARP1) plays a very important role in the DNA damage response, but its role in numerous aspects is not fully understood. We recently showed that in the absence of DNA damage, PARP1 regulates the expression of the chromatin-modifying enzyme EZH2. Work from other groups has shown that EZH2 participates in the DNA damage response. These combined data suggest that EZH2 could be a target of PARP1 in both untreated and genotoxic agent-treated conditions. In this work we tested the hypothesis that, in response to DNA damage, PARP1 regulates EZH2 activity. Here we report that PARP1 regulates EZH2 activity after DNA damage. In particular, we find that EZH2 is a direct target of PARP1 upon induction of alkylating and UV-induced DNA damage in cells andin vitro. PARylation of EZH2 inhibits EZH2 histone methyltransferase (H3K27me) enzymatic activity. We observed in cells that the induction of PARP1 activity by DNA alkylating agents decreases the association of EZH2 with chromatin, and PARylation of histone H3 reduces EZH2 affinity for its target histone H3. Our findings establish that PARP1 and PARylation are important regulators of EZH2 function and link EZH2-mediated heterochromatin formation, DNA damage and PARylation. These findings may also have clinical implications, as they suggest that inhibitors of EZH2 can improve anti-tumor effects of PARP1 inhibitors in BRCA1/2-deficient cancers.

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X Demographics

The data shown below were collected from the profiles of 2 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 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 36 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 22%
Student > Ph. D. Student 6 17%
Student > Bachelor 4 11%
Student > Postgraduate 3 8%
Student > Master 2 6%
Other 6 17%
Unknown 7 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 36%
Agricultural and Biological Sciences 5 14%
Medicine and Dentistry 3 8%
Immunology and Microbiology 2 6%
Chemistry 2 6%
Other 2 6%
Unknown 9 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 28 January 2021.
All research outputs
#7,408,974
of 24,387,992 outputs
Outputs from Oncotarget
#3,272
of 14,160 outputs
Outputs of similar age
#143,272
of 449,721 outputs
Outputs of similar age from Oncotarget
#127
of 552 outputs
Altmetric has tracked 24,387,992 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 14,160 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one has done well, scoring higher than 76% 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 449,721 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 552 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.