Evidence map›Paper›PMID 33210317›Full record

ArticleThe EMBO journal2021

Human CST complex protects stalled replication forks by directly blocking MRE11 degradation of nascent-strand DNA.

Xinxing Lyu, Kai-Hang Lei, Pau Biak Sang, Olga Shiva, Megan Chastain, Peter Chi, Weihang Chai

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

50 citing papers in PubMed, 61 citations in OpenAlex.

  1. Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026
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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

7 authors at 3 institutions in 2 countries.

Xinxing LyuDepartment of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA.
Kai-Hang LeiInstitute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.ORCID 0000-0002-8783-5806
Pau Biak SangDepartment of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA.
Olga ShivaDepartment of Biomedical Sciences, ESF College of Medicine, Washington State University, Spokane, WA, USA.
Megan ChastainDepartment of Biomedical Sciences, ESF College of Medicine, Washington State University, Spokane, WA, USA.
Peter ChiInstitute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.ORCID 0000-0001-9229-8729
Weihang ChaiDepartment of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA.ORCID 0000-0003-1206-2324
Washington State University Spokane · USLoyola University Chicago · USNational Taiwan University · TW

Funding

Molecular Modulator of RPA and RAD51 in Maintaining Genome StabilityR01CA234266 · NCI · WASHINGTON STATE UNIVERSITY · PI Weihang Chai · 2019 to 2026
$2.4M
Mechanisms of Fork Restart in Response to Genotoxic StressR01GM112864 · NIGMS · WASHINGTON STATE UNIVERSITY · PI CHAI, WEIHANG · 2014 to 2018
$1.5M
NCI NIH HHS R01 CA234266NIGMS NIH HHS R01 GM112864Taiwan ministry of Science Technology MOST 108-2321-B-002-054
6 · The paper itself

Abstract

Degradation and collapse of stalled replication forks are main sources of genomic instability, yet the molecular mechanisms for protecting forks from degradation/collapse are not well understood. Here, we report that human CST (CTC1-STN1-TEN1) proteins, which form a single-stranded DNA-binding complex, localize at stalled forks and protect stalled forks from degradation by the MRE11 nuclease. CST deficiency increases MRE11 binding to stalled forks, leading to nascent-strand degradation at reversed forks and ssDNA accumulation. In addition, purified CST complex binds to 5' DNA overhangs and directly blocks MRE11 degradation in vitro, and the DNA-binding ability of CST is required for blocking MRE11-mediated nascent-strand degradation. Our results suggest that CST inhibits MRE11 binding to reversed forks, thus antagonizing excessive nascent-strand degradation. Finally, we uncover that CST complex inactivation exacerbates genome instability in BRCA2 deficient cells. Collectively, our findings identify the CST complex as an important fork protector that preserves genome integrity under replication perturbation.

Indexed as

Cell LineCell Line, TumorDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA HelicasesDNA RepairDNA ReplicationDNA, Single-StrandedHCT116 CellsHEK293 CellsHeLa CellsHumansMRE11 Homologue ProteinProtein BindingTelomere-Binding ProteinsCtc1 protein, humanDNA-Binding ProteinsDNA HelicasesDNA, Single-StrandedMRE11 Homologue ProteinMRE11 protein, humanStn1 protein, humanTelomere-Binding ProteinsTen1 protein, humanCST complexDNA degradationgenome stabilitynascent strandreplication stress

Identifiers

PMID33210317
PMCPMC7809791
OpenAlexW3100525765

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.