Evidence map›Paper›PMID 27672210›Full record

ArticleThe Journal of biological chemistry2016

Class I Histone Deacetylase HDAC1 and WRN RECQ Helicase Contribute Additively to Protect Replication Forks upon Hydroxyurea-induced Arrest.

Keffy Kehrli, Michael Phelps, Pavlo Lazarchuk, Eleanor Chen, Ray Monnat, Julia M Sidorova

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

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  16. Article
  17. Werner Syndrome Protein and DNA Replication.International journal of molecular sciences · 2018
    Review
  18. Review
  19. Article
  20. Review
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

6 authors at 1 institution in 1 country.

Keffy KehrliFrom the Department of Pathology and.
Michael PhelpsFrom the Department of Pathology and.
Pavlo LazarchukFrom the Department of Pathology and.
Eleanor ChenFrom the Department of Pathology and.
Ray MonnatFrom the Department of Pathology and; Department of Genome Sciences, University of Washington, Seattle, Washington 98195.
Julia M SidorovaFrom the Department of Pathology and. Electronic address: julias@uw.edu.
University of Washington · US

Funding

Tumor mutation signaturesP01CA077852 · NCI · UNIVERSITY OF WASHINGTON · PI SIDOROVA, JULIA · 1999 to 2019
$26.0M
Epigenetics of replication stress in human cellsR01GM115482 · NIGMS · UNIVERSITY OF WASHINGTON · PI SIDOROVA, JULIA · 2016 to 2020
$1.6M
Characterizing Histone Deacetylases in RhabdomyosarcomaR01CA196882 · NCI · UNIVERSITY OF WASHINGTON · PI CHEN, ELEANOR Y · 2016 to 2020
$1.6M
Druggable Pathways Regulating Self-Renewal in Muscle and Rhabdomyosarcoma.K08AR063165 · NIAMS · UNIVERSITY OF WASHINGTON · PI CHEN, ELEANOR Y · 2012 to 2016
$694k
NCI NIH HHS P01 CA077852NCI NIH HHS R01 CA196882NIAMS NIH HHS K08 AR063165NIGMS NIH HHS R01 GM115482
6 · The paper itself

Abstract

The WRN helicase/exonuclease is mutated in Werner syndrome of genomic instability and premature aging. WRN-depleted fibroblasts, although remaining largely viable, have a reduced capacity to maintain replication forks active during a transient hydroxyurea-induced arrest. A strand exchange protein, RAD51, is also required for replication fork maintenance, and here we show that recruitment of RAD51 to stalled forks is reduced in the absence of WRN. We performed a siRNA screen for genes that are required for viability of WRN-depleted cells after hydroxyurea treatment, and identified HDAC1, a member of the class I histone deacetylase family. One of the functions of HDAC1, which it performs together with a close homolog HDAC2, is deacetylation of new histone H4 deposited at replication forks. We show that HDAC1 depletion exacerbates defects in fork reactivation and progression after hydroxyurea treatment observed in WRN- or RAD51-deficient cells. The additive WRN, HDAC1 loss-of-function phenotype is also observed with a catalytic mutant of HDAC1; however, it does not correlate with changes in histone H4 deacetylation at replication forks. On the other hand, inhibition of histone deacetylation by an inhibitor specific to HDACs 1-3, CI-994, correlates with increased processing of newly synthesized DNA strands in hydroxyurea-stalled forks. WRN co-precipitates with HDAC1 and HDAC2. Taken together, our findings indicate that WRN interacts with HDACs 1 and 2 to facilitate activity of stalled replication forks under conditions of replication stress.

Indexed as

Cell Cycle CheckpointsCell Line, TransformedDNA ReplicationHistone Deacetylase 1Histone Deacetylase 2Histone Deacetylase 3Histone DeacetylasesHumansHydroxyureaRad51 RecombinaseWerner Syndrome HelicaseHDAC1 protein, humanHDAC2 protein, humanHistone Deacetylase 1Histone Deacetylase 2Histone Deacetylase 3Histone DeacetylasesHydroxyureaRAD51 protein, humanRad51 RecombinaseWerner Syndrome HelicaseWRN protein, humanDNA helicaseDNA replicationhistone acetylationhistone deacetylase 1 (HDAC1)humansmall interfering RNA (siRNA)tissue cultureWerner syndrome protein

Identifiers

PMID27672210
PMCPMC5114403
OpenAlexW2527157192

What OpenQuestion holds

Textmetadata
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.