Evidence map›Paper›PMID 24947512›Full record

ArticleThe Journal of biological chemistry2014

Thymine DNA glycosylase is a CRL4Cdt2 substrate.

Tamara J Slenn, Benjamin Morris, Courtney G Havens, Robert M Freeman, Tatsuro S Takahashi, Johannes C Walter

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

35 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. STK19 positions TFIIH for cell-free transcription-coupled DNA repair.bioRxiv : the preprint server for biology · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Revisiting the Function of p21International journal of molecular sciences · 2022
    Review
  9. Article
  10. CRL4Genes · 2022
    Review
  11. Regulation of DNA Replication Licensing and Re-Replication by Cdt1.International journal of molecular sciences · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation.Journal of experimental & clinical cancer research : CR · 2019
    Article
  18. Defining the Role of Nucleotide Flipping in Enzyme Specificity UsingJournal of the American Chemical Society · 2019
    Article
  19. Article
  20. Article
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

6 authors at 3 institutions in 2 countries.

Tamara J SlennDepartments of Biological Chemistry and Molecular Pharmacology and Harvard Medical School, Boston, Massachusetts 02115.
Benjamin MorrisDepartments of Biological Chemistry and Molecular Pharmacology and Harvard Medical School, Boston, Massachusetts 02115.
Courtney G HavensDepartments of Biological Chemistry and Molecular Pharmacology and Harvard Medical School, Boston, Massachusetts 02115.
Robert M FreemanDepartments of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115.
Tatsuro S TakahashiGraduate School of Science, Osaka University, Osaka, Japan, and.
Johannes C WalterDepartments of Biological Chemistry and Molecular Pharmacology and Harvard Medical School, Boston, Massachusetts 02115; Howard Hughes Medical Institute, Harvard University, Boston, Massachusetts 02115. Electronic address: johannes_walter@hms.harvard.edu.
Harvard University · USHoward Hughes Medical Institute · USOsaka University · JP

Funding

BIOCHEMICAL STUDIES OF MITOSISR01GM026875 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI KIRSCHNER, MARC WALLACE · 1985 to 2019
$18.2M
Training in Molecular, Cellular, and Chemical BiologyT32GM007598 · NIGMS · HARVARD UNIVERSITY · PI DULAC, CATHERINE · 1985 to 2019
$16.2M
The mechanism of vertebrate DNA replication terminationR01GM080676 · NIGMS · HARVARD MEDICAL SCHOOL · PI WALTER, JOHANNES · 2007 to 2019
$3.7M
BIOCHEMICAL STUDIES OF MITOSISR37GM026875 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI KIRSCHNER, MARC W · 1986 to 1995
–
Howard Hughes Medical InstituteNIGMS NIH HHS GM26875NIGMS NIH HHS GM80676NIGMS NIH HHS R01 GM026875NIGMS NIH HHS R01 GM080676NIGMS NIH HHS T32 GM007598
6 · The paper itself

Abstract

The E3 ubiquitin ligase CRL4(Cdt2) targets proteins for destruction in S phase and after DNA damage by coupling ubiquitylation to DNA-bound proliferating cell nuclear antigen (PCNA). Coupling to PCNA involves a PCNA-interacting peptide (PIP) degron motif in the substrate that recruits CRL4(Cdt2) while binding to PCNA. In vertebrates, CRL4(Cdt2) promotes degradation of proteins whose presence in S phase is deleterious, including Cdt1, Set8, and p21. Here, we show that CRL4(Cdt2) targets thymine DNA glycosylase (TDG), a base excision repair enzyme that is involved in DNA demethylation. TDG contains a conserved and nearly perfect match to the PIP degron consensus. TDG is ubiquitylated and destroyed in a PCNA-, Cdt2-, and PIP degron-dependent manner during DNA repair in Xenopus egg extract. The protein can also be destroyed during DNA replication in this system. During Xenopus development, TDG first accumulates during gastrulation, and its expression is down-regulated by CRL4(Cdt2). Our results expand the group of vertebrate CRL4(Cdt2) substrates to include a bona fide DNA repair enzyme.

Indexed as

AnimalsDNA MethylationGastrulaGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicThymine DNA GlycosylaseUbiquitinationUbiquitin-Protein Ligase ComplexesUbiquitin-Protein LigasesXenopus laevisXenopus Proteinsdtl protein, XenopusThymine DNA GlycosylaseUbiquitin-Protein Ligase ComplexesUbiquitin-Protein LigasesXenopus ProteinsBase Excision Repair (BER)CRL4-Cdt2DNA MethylationDNA ReplicationE3 Ubiquitin LigaseProteolysisThymine DNA Glycosylase (TDG)Xenopus

Identifiers

PMID24947512
PMCPMC4132803
OpenAlexW2014867464

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.