Evidence map›Paper›PMID 20660159›Full record

ArticleMolecular biology of the cell2010

Ubc4 and Not4 regulate steady-state levels of DNA polymerase-α to promote efficient and accurate DNA replication.

Justin Haworth, Robert C Alver, Melissa Anderson, Anja-Katrin Bielinsky

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. MCM10: one tool for all-Integrity, maintenance and damage control.Seminars in cell & developmental biology · 2014
    Review
  11. Article
  12. Enigmatic roles of Mcm10 in DNA replication.Trends in biochemical sciences · 2013
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Ccr4-Not complex: the control freak of eukaryotic cells.Critical reviews in biochemistry and molecular biology
    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

4 authors at 2 institutions in 1 country.

Justin HaworthDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Robert C Alver
Melissa Anderson
Anja-Katrin Bielinsky
University of Minnesota · USColumbia University · US

Funding

TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
Understanding the biological function of Mcm10 in yeastR01GM074917 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BIELINSKY, ANJA-KATRIN · 2005 to 2019
$3.7M
NCI NIH HHS CA009138NCI NIH HHS T32 CA009138NIGMS NIH HHS GM074917NIGMS NIH HHS R01 GM074917
6 · The paper itself

Abstract

The accurate duplication of chromosomal DNA is required to maintain genomic integrity. However, from an evolutionary point of view, a low mutation rate during DNA replication is desirable. One way to strike the right balance between accuracy and limited mutagenesis is to use a DNA polymerase that lacks proofreading activity but contributes to DNA replication in a very restricted manner. DNA polymerase-α fits this purpose exactly, but little is known about its regulation at the replication fork. Minichromosome maintenance protein (Mcm) 10 regulates the stability of the catalytic subunit of pol-α in budding yeast and human cells. Cdc17, the catalytic subunit of pol-α in yeast, is rapidly degraded after depletion of Mcm10. Here we show that Ubc4 and Not4 are required for Cdc17 destabilization. Disruption of Cdc17 turnover resulted in sensitivity to hydroxyurea, suggesting that this pathway is important for DNA replication. Furthermore, overexpression of Cdc17 in ubc4 and not4 mutants caused slow growth and synthetic dosage lethality, respectively. Our data suggest that Cdc17 levels are very tightly regulated through the opposing forces of Ubc4 and Not4 (destabilization) and Mcm10 (stabilization). We conclude that regular turnover of Cdc17 via Ubc4 and Not4 is required for proper cell proliferation.

Indexed as

DNA ReplicationCell Cycle ProteinsCell NucleusCell ProliferationChromosomal Proteins, Non-HistoneDNA Polymerase IGenomic InstabilityHumansMinichromosome Maintenance ProteinsMutationProteasome Endopeptidase ComplexRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesCell Cycle ProteinsChromosomal Proteins, Non-HistoneDNA Polymerase IMCM10 protein, humanMCM10 protein, S cerevisiaeMinichromosome Maintenance ProteinsMOT2 protein, S cerevisiaePOL1 protein, S cerevisiaeProteasome Endopeptidase ComplexRepressor ProteinsSaccharomyces cerevisiae ProteinsUbc4 protein, S cerevisiaeUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID20660159
PMCPMC2938386
OpenAlexW2096077105

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.