Evidence map›Paper›PMID 30237520›Full record

ArticleScientific reports2018

Cellular Depletion of BRD8 Causes p53-Dependent Apoptosis and Induces a DNA Damage Response in Non-Stressed Cells.

Anahita Lashgari, Myriam Fauteux, Alexandre Maréchal, Luc Gaudreau

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Anahita LashgariDépartement de biologie, Université de Sherbrooke, 2500 Boulevard de l'Université, Sherbrooke, QC, J1K 2R1, Canada.
Myriam FauteuxDépartement de biologie, Université de Sherbrooke, 2500 Boulevard de l'Université, Sherbrooke, QC, J1K 2R1, Canada.
Alexandre MaréchalDépartement de biologie, Université de Sherbrooke, 2500 Boulevard de l'Université, Sherbrooke, QC, J1K 2R1, Canada.
Luc GaudreauDépartement de biologie, Université de Sherbrooke, 2500 Boulevard de l'Université, Sherbrooke, QC, J1K 2R1, Canada. Luc.Gaudreau@USherbrooke.ca.
Université de Sherbrooke · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regulation of the chromatin state is crucial for biological processes such as the regulation of transcription, DNA replication, and DNA damage repair. Here we show that knockdown of the BRD8 bromodomain protein - a subunit of the p400/Tip60 complex - leads to p21 induction, and concomitant cell cycle arrest in G1/S. We further demonstrate that the p53 transcriptional pathway is activated in BRD8-depleted cells, and this accounts for upregulation of not only p21 but also of pro-apoptotic genes, leading to subsequent apoptosis. Importantly, the DNA damage response (DDR) is induced upon BRD8 depletion, and DNA damage foci are detectable in BRD8-depleted cells under normal growth conditions. Consistently with an activated DDR, we find that in BRD8-depleted cells, the ATM-CHK2 DDR pathway is turned on but, CHK1 proteins levels are severely reduced and replication stress is detectable as enhanced replication protein A (RPA32) phosphorylation levels. Notably, acetylation of histone H4 at K16 (H4K16ac) is reduced in BRD8-depleted cells, suggesting that BRD8 may have a role in the recruitment and/or stabilization of the p400/Tip60 complex within chromatin, thereby facilitating DNA repair. Taken together, our results suggest that BRD8 is involved not only in p53-dependent gene suppression, but also in the maintenance of genome stability.

Indexed as

ApoptosisBromodomain Containing ProteinsCell Cycle CheckpointsCell Line, TumorCell ProliferationDNA DamageHumansPhosphorylationReceptors, Thyroid HormoneSignal TransductionTranscription FactorsTumor Suppressor Protein p53BRD8 protein, humanBromodomain Containing ProteinsReceptors, Thyroid HormoneTranscription FactorsTumor Suppressor Protein p53

Identifiers

PMID30237520
PMCPMC6147888
OpenAlexW2889768017

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.