Evidence map›Paper›PMID 25918225›Full record

ArticleThe Journal of cell biology2015

Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing.

Yihan Wan, Xiaobin Zheng, Haiyang Chen, Yuxuan Guo, Hao Jiang, Xiaonan He, Xueliang Zhu, Yixian Zheng

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

48 citing papers in PubMed, 89 citations in OpenAlex.

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  7. The varied functions of the giant muscle scaffold protein obscurin.Frontiers in cell and developmental biology · 2025
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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

8 authors at 3 institutions in 2 countries.

Yihan WanState Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
Xiaobin ZhengDepartment of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
Haiyang ChenDepartment of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
Yuxuan GuoDepartment of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
Hao JiangState Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
Xiaonan HeState Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xueliang ZhuState Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China zheng@ciwemb.edu xlzhu@sibcb.ac.cn.
Yixian ZhengDepartment of Embryology, Carnegie Institution for Science, Baltimore, MD 21218 zheng@ciwemb.edu xlzhu@sibcb.ac.cn.
Carnegie Institution for Science · USCenter for Excellence in Molecular Cell Science · CNChinese Academy of Sciences · CN

Funding

The function and assembly of the lamin-B spindle sheathR01GM056312 · NIGMS · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · PI ZHENG, YIXIAN · 1997 to 2014
$2.7M
Mechanisms of chromosome segregation and mitotic timingR01GM110151 · NIGMS · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · PI ZHENG, YIXIAN · 2015 to 2018
$1.5M
NIGMS NIH HHS R01 GM056312NIGMS NIH HHS R01 GM06023NIGMS NIH HHS R01 GM110151
6 · The paper itself

Abstract

Although studies suggest that perturbing mitotic progression leads to DNA damage and p53 activation, which in turn lead to either cell apoptosis or senescence, it remains unclear how mitotic defects trigger p53 activation. We show that BuGZ and Bub3, which are two mitotic regulators localized in the interphase nucleus, interact with the splicing machinery and are required for pre-mRNA splicing. Similar to inhibition of RNA splicing by pladienolide B, depletion of either BuGZ or Bub3 led to increased formation of RNA-DNA hybrids (R-loops), which led to DNA damage and p53 activation in both human tumor cells and primary cells. Thus, R-loop-mediated DNA damage and p53 activation offer a mechanistic explanation for apoptosis of cancer cells and senescence of primary cells upon disruption of the dual-function mitotic regulators. This demonstrates the importance of understanding the full range of functions of mitotic regulators to develop antitumor drugs.

Indexed as

ApoptosisDNA DamageRNA SplicingAnimalsBiomarkersBlotting, WesternCell Cycle ProteinsCellular SenescenceDrosophila melanogasterFibroblastsFluorescent Antibody TechniqueHigh-Throughput Nucleotide SequencingHumansImmunoprecipitationMicrotubule-Associated ProteinsMitosisBiomarkersBUB3 protein, humanCell Cycle ProteinsMicrotubule-Associated ProteinsPoly-ADP-Ribose Binding ProteinsRNA, MessengerTP53 protein, humanTumor Suppressor Protein p53ZNF207 protein, human

Identifiers

PMID25918225
PMCPMC4411280
OpenAlexW2124152741

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.