Evidence map›Paper›PMID 40475552›Full record

ArticlebioRxiv : the preprint server for biology2025

The Mediator Kinase Module regulates cell cycle re-entry and transcriptional responses following DNA damage.

Gönen Memişoğlu, Stefan Bohn, Nevan J Krogan, James E Haber, Alexander J Ruthenburg

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Gönen MemişoğluDepartment of Molecular Genetics and Cell Biology, The University of Chicago, IL, 60637, USA.ORCID 0000-0002-2901-3150
Stefan BohnQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.
Nevan J KroganQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.
James E HaberDepartment of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA, 02454, USA.
Alexander J RuthenburgDepartment of Molecular Genetics and Cell Biology, The University of Chicago, IL, 60637, USA.

Funding

The Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trey Ideker · 2022 to 2026
$14.2M
DNA Damage Response and Repair of a Broken ChromosomeR35GM127029 · NIGMS · BRANDEIS UNIVERSITY · PI JAMES E HABER · 2018 to 2026
$8.6M
Comparative Analysis of Genetic Interaction NetworksR01GM084279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY, KROGAN, NEVAN J · 2008 to 2017
$3.9M
Defining the mechanisms of epigenetic information flowR35GM145373 · NIGMS · UNIVERSITY OF CHICAGO · PI Alexander Jackson Ruthenburg · 2022 to 2026
$2.1M
Elucidating the mechanisms of non-canonical CDK8 function in DNA damage signalingF32GM145156 · NIGMS · UNIVERSITY OF CHICAGO · PI MEMISOGLU, GONEN · 2022 to 2023
$144k
NCI NIH HHS U54 CA274502NIGMS NIH HHS F32 GM145156NIGMS NIH HHS R01 GM084279NIGMS NIH HHS R35 GM127029NIGMS NIH HHS R35 GM145373
6 · The paper itself

Abstract

The Cdk8 kinase module (CKM) is a non-obligate and dissociable subcomplex of Mediator of transcription, a key regulator of RNA polymerase II (RNAPII). Through a genetic screen in yeast, we discovered a surprising role for Mediator CKM in the DNA damage response (DDR) and mitotic re-entry. Remarkably, we find that a single DNA break is sufficient for CKM-dependent global transcriptional attenuation. Upon DDR activation, the kinase activity of CKM antagonizes RNAPII binding to core Mediator, thereby reducing the transcriptionally-engaged RNAPII pool. This transcriptional attenuation is essential for DDR inactivation and limits the spreading of γ-H2AX into gene bodies. Furthermore, CKM localizes to DNA breaks to impede RNAPII binding. Importantly, we demonstrate that the role of CKM on DDR and transcriptional attenuation is conserved from yeast to mammals, establishing a multifaceted and essential function for CKM in transcriptional regulation of DNA-damage response.

Indexed as

Cdk8 Kinase ModuleDNA damage responseMediator of TranscriptionRNAPII

Identifiers

PMID40475552
PMCPMC12139960

What OpenQuestion holds

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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.