Evidence map›Paper›PMID 38554706›Full record

ArticleCell2024

The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.

Vidhya Krishnamoorthy, Martina Foglizzo, Robert L Dilley, Angela Wu, Arindam Datta, Parul Dutta, Lisa J Campbell, Oksana Degtjarik, Laura J Musgrove, Antonio N Calabrese and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Structural Activation of DNA Unwinding by MCM8/9/HROB.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Observational
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
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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

12 authors at 3 institutions in 2 countries.

Vidhya KrishnamoorthyDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Martina FoglizzoAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Robert L DilleyDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. Electronic address: rdilley4@gmail.com.
Angela WuDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Arindam DattaDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Parul DuttaDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Lisa J CampbellAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Oksana DegtjarikAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Laura J MusgroveAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Antonio N CalabreseAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Elton ZeqirajAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. Electronic address: e.zeqiraj@leeds.ac.uk.
Roger A GreenbergDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. Electronic address: rogergr@pennmedicine.upenn.edu.
University of Leeds · GBUniversity of Pennsylvania · USPenn Center for AIDS Research · US

Funding

Tumor cell instrinsic DNA damage signaling to the immune responseP01CA265794 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Roger A Greenberg · 2023 to 2026
$8.5M
Roles of Chromatin Modification in BRCA1 Dependent DNA RepairR01CA174904 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Roger A Greenberg · 2013 to 2026
$4.8M
DNA Double Strand Break Chromatin Alterations and Genome IntegrityR01GM101149 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GREENBERG, ROGER A · 2013 to 2025
$4.0M
Discovery of Chemical Probes for RNA-Binding Protein Host Defense FactorsR01GM110119 · NIGMS · OYAGEN, INC. · PI SMITH, HAROLD C · 2015 to 2017
$1.8M
Medical Research Council MR/T029471/1NCI NIH HHS P01 CA265794NCI NIH HHS R01 CA174904NIGMS NIH HHS R01 GM101149NIGMS NIH HHS R01 GM110119Wellcome Trust 220628Wellcome Trust 223810
6 · The paper itself

Abstract

Ubiquitin-dependent unfolding of the CMG helicase by VCP/p97 is required to terminate DNA replication. Other replisome components are not processed in the same fashion, suggesting that additional mechanisms underlie replication protein turnover. Here, we identify replisome factor interactions with a protein complex composed of AAA+ ATPases SPATA5-SPATA5L1 together with heterodimeric partners C1orf109-CINP (55LCC). An integrative structural biology approach revealed a molecular architecture of SPATA5-SPATA5L1 N-terminal domains interacting with C1orf109-CINP to form a funnel-like structure above a cylindrically shaped ATPase motor. Deficiency in the 55LCC complex elicited ubiquitin-independent proteotoxicity, replication stress, and severe chromosome instability. 55LCC showed ATPase activity that was specifically enhanced by replication fork DNA and was coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. These findings define 55LCC-mediated proteostasis as critical for replication fork progression and genome stability and provide a rationale for pathogenic variants seen in associated human neurodevelopmental disorders.

Indexed as

Adenosine TriphosphatasesDNA ReplicationGenomic InstabilityProteostasisATPases Associated with Diverse Cellular ActivitiesCell Cycle ProteinsHEK293 CellsHumansValosin Containing ProteinAdenosine TriphosphatasesATPases Associated with Diverse Cellular ActivitiesCell Cycle ProteinsValosin Containing Protein55LCCAAA+ ATPaseC1orf109CINPgenome instabilityreplication stress responsereplisome regulation/proteostasisSPATA5SPATA5L1unfoldase

Identifiers

PMID38554706
PMCPMC11055677
OpenAlexW4393307771

What OpenQuestion holds

Textmetadata
LicenceTDM
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.