Evidence map›Paper›PMID 30595436›Full record

ArticleMolecular cell2019

Replication-Coupled DNA-Protein Crosslink Repair by SPRTN and the Proteasome in Xenopus Egg Extracts.

Nicolai B Larsen, Alan O Gao, Justin L Sparks, Irene Gallina, R Alex Wu, Matthias Mann, Markus Räschle, Johannes C Walter, Julien P Duxin

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

125 citing papers in PubMed, 193 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

65 more citing papers are in PubMed but not listed here.

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

9 authors at 6 institutions in 3 countries.

Nicolai B LarsenFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Alan O GaoFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Justin L SparksDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Irene GallinaFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark.
R Alex WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Matthias MannFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Markus RäschleDepartment of Molecular Biotechnology and Systems Biology, Technical University of Kaiserslautern, 67653 Kaiserslautern, Germany.
Johannes C WalterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: johannes_walter@hms.harvard.edu.
Julien P DuxinFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: julien.duxin@cpr.ku.dk.
Harvard University · USNovo Nordisk Foundation · DKUniversity of Copenhagen · DKHoward Hughes Medical Institute · USMax Planck Institute of Biochemistry · DEUniversity of Kaiserslautern · DE

Funding

The Fanconi anemia pathway: role in DNA interstrand cross-link repairR01HL098316 · NHLBI · HARVARD MEDICAL SCHOOL · PI Johannes Walter · 2010 to 2026
$6.3M
NHLBI NIH HHS R01 HL098316
6 · The paper itself

Abstract

DNA-protein crosslinks (DPCs) are bulky lesions that interfere with DNA metabolism and therefore threaten genomic integrity. Recent studies implicate the metalloprotease SPRTN in S phase removal of DPCs, but how SPRTN is targeted to DPCs during DNA replication is unknown. Using Xenopus egg extracts that recapitulate replication-coupled DPC proteolysis, we show that DPCs can be degraded by SPRTN or the proteasome, which act as independent DPC proteases. Proteasome recruitment requires DPC polyubiquitylation, which is partially dependent on the ubiquitin ligase activity of TRAIP. In contrast, SPRTN-mediated DPC degradation does not require DPC polyubiquitylation but instead depends on nascent strand extension to within a few nucleotides of the lesion, implying that polymerase stalling at the DPC activates SPRTN on both leading and lagging strand templates. Our results demonstrate that SPRTN and proteasome activities are coupled to DNA replication by distinct mechanisms that promote replication across immovable protein barriers.

Indexed as

DNA RepairDNA ReplicationAnimalsDNAFemaleMaleNucleic Acid ConformationProteasome Endopeptidase ComplexProtein Interaction Domains and MotifsProteolysisSf9 CellsStructure-Activity RelationshipUbiquitinationXenopus laevisXenopus ProteinsDNAProteasome Endopeptidase ComplexXenopus ProteinsDNA-portein crosslink (DPC)DNA repairDNA replicationProteasomeSPRTNTRAIPtranslesion synthesis (TLS)Ubiquitin

Identifiers

PMID30595436
PMCPMC6375733
OpenAlexW2908352025

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.