Evidence map›Paper›PMID 23913683›Full record

ArticleThe Journal of biological chemistry2013

A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase δ in response to DNA damage and during the S phase.

Sufang Zhang, Hong Zhao, Zbiegniew Darzynkiewicz, Pengbo Zhou, Zhongtao Zhang, Ernest Y C Lee, Marietta Y W T Lee

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.7field-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

43 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Canonical binding ofFrontiers in molecular biosciences · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Regulation of DNA Replication Licensing and Re-Replication by Cdt1.International journal of molecular sciences · 2021
    Review
  9. Beyond the Lesion: Back to High Fidelity DNA Synthesis.Frontiers in molecular biosciences · 2021
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019
    Review
  17. Article
  18. Review
  19. Article
  20. Review
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 2 institutions in 1 country.

Sufang ZhangFrom the Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595.
Hong Zhao
Zbiegniew Darzynkiewicz
Pengbo Zhou
Zhongtao Zhang
Ernest Y C Lee
Marietta Y W T Lee
New York Medical College · USCornell University · US

Funding

PROBES FOR FLOW CYTOMETRYR01CA028704 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI DARZYNKIEWICZ, ZBIGNIEW · 1985 to 2014
$6.0M
BIOCHEMICAL STUDIES OF POLYMERASE DELTAR01GM031973 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEE, MARIETTA Y. · 1985 to 2012
$5.8M
Modification of DNA Polymerase Delta by a Novel Mechanism During Replication StreR01ES014737 · NIEHS · NEW YORK MEDICAL COLLEGE · PI LEE, MARIETTA Y., ZHANG, ZHONGTAO · 2008 to 2017
$3.5M
Regulation of Nucleotide Excision Repair by ProteolysisR01CA098210 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI ZHOU, PENGBO · 2003 to 2013
$3.3M
Tumorigenic Role of the CUL4A Ubiquitin LigaseR01CA159925 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SHIN, SANDRA, ZHOU, PENGBO · 2011 to 2015
$2.0M
Regulation of Nucleotide Excision Repair by ProteolysisR56CA098210 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI ZHOU, PENGBO · 2008 to 2008
$329k
NCI NIH HHS CA028704NCI NIH HHS CA098210NCI NIH HHS CA159925NCI NIH HHS R01 CA028704NCI NIH HHS R01 CA098210NCI NIH HHS R01 CA159925NCI NIH HHS R56 CA098210NIEHS NIH HHS ES14737NIEHS NIH HHS R01 ES014737NIGMS NIH HHS GM31973NIGMS NIH HHS R01 GM031973
6 · The paper itself

Abstract

DNA polymerase δ (Pol δ4) is a heterotetrameric enzyme, whose p12 subunit is degraded in response to DNA damage, leaving behind a trimer (Pol δ3) with altered enzymatic characteristics that participate in gap filling during DNA repair. We demonstrate that CRL4(Cdt2), a key regulator of cell cycle progression that targets replication licensing factors, also targets the p12 subunit of Pol δ4 in response to DNA damage and on entry into S phase. Evidence for the involvement of CRL4(Cdt2) included demonstration that p12 possesses a proliferating cell nuclear antigen-interacting protein-degron (PIP-degron) and that knockdown of the components of the CRL4(Cdt2) complex inhibited the degradation of p12 in response to DNA damage. Analysis of p12 levels in synchronized cell populations showed that p12 is partially degraded in S phase and that this is affected by knockdowns of CUL4A or CUL4B. Laser scanning cytometry of overexpressed wild type p12 and a mutant resistant to degradation showed that the reduction in p12 levels during S phase was prevented by mutation of p12. Thus, CRL4(Cdt2) also regulates the subunit composition of Pol δ during the cell cycle. These studies reveal a novel function of CRL4(Cdt2), i.e. the direct regulation of DNA polymerase δ, adding to its known functions in the regulation of the licensing of replication origins and expanding the scope of its overall control of DNA replication. The formation of Pol δ3 in S phase as a normal aspect of cell cycle progression leads to the novel implications that it is involved in DNA replication as well as DNA repair.

Indexed as

DNA DamageS PhaseAmino Acid SequenceBinding SitesBlotting, WesternCell Line, TumorCullin ProteinsDNA Polymerase IIIHEK293 CellsHeLa CellsHumansLaser Scanning CytometryModels, MolecularMolecular Sequence DataMutationNuclear ProteinsCUL4A protein, humanCUL4B protein, humanCullin ProteinsDNA Polymerase IIIDTL protein, humanNuclear ProteinsPOLD4 protein, humanProtein SubunitsUbiquitin-Protein LigasesCell CycleDNA Damage ResponseDNA PolymeraseDNA RepairDNA ReplicationUbiquitin Ligase

Identifiers

PMID23913683
PMCPMC3795253
OpenAlexW2050445393

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.