Evidence map›Paper›PMID 20010813›Full record

ArticleNature cell biology2010

Defects in DNA ligase I trigger PCNA ubiquitylation at Lys 107.

Sapna Das-Bradoo, Hai Dang Nguyen, Jamie L Wood, Robin M Ricke, Justin C Haworth, Anja-Katrin Bielinsky

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

46 citing papers in PubMed, 70 citations in OpenAlex.

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

Sapna Das-BradooUniversity of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, MN 55455, USA.
Hai Dang Nguyen
Jamie L Wood
Robin M Ricke
Justin C Haworth
Anja-Katrin Bielinsky
University of Minnesota · USMayo Clinic in Florida · US

Funding

XRAY CRYSTALLOGRAPHIC STRUCTURE ANALYSIS: PROTEIN SORTINGP41RR001081 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COHEN, BRUCE E · 1985 to 2011
$17.6M
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 CA009138NCRR NIH HHS P41 RR001081NCRR NIH HHS P41 RR-01081NIGMS NIH HHS GM074917NIGMS NIH HHS R01 GM074917
6 · The paper itself

Abstract

In all eukaryotes, the ligation of newly synthesized DNA, also known as Okazaki fragments, is catalysed by DNA ligase I (ref. 1). An individual with a DNA ligase I deficiency exhibits growth retardation, sunlight sensitivity and severe immunosuppression, probably due to accumulation of DNA damage. Surprisingly, not much is known about the DNA damage response (DDR) in DNA ligase I-deficient cells. As DNA replication and DDR pathways are highly conserved in eukaryotes, we used Saccharomyces cerevisiae as a model system to address this issue. We uncovered a new pathway, which facilitates ubiquitylation at Lys 107 of proliferating cell nuclear antigen (PCNA). Unlike ubiquitylation at Lys 164 of PCNA in response to UV irradiation, which triggers translesion synthesis, modification of Lys 107 is not dependent on the ubiquitin conjugating enzyme (E2) Rad6 (ref. 4) nor the ubiquitin ligase (E3) Rad18 (ref. 5), but requires the E2 variant Mms2 (ref. 6) in conjunction with Ubc4 (ref. 7) and the E3 Rad5 (Refs 8, 9). Surprisingly, DNA ligase I-deficient S. cerevisiae cdc9-1 cells that carry a PCNAK107R mutation are inviable, because they cannot activate a robust DDR. Furthermore, we show that ubiquitylation of PCNA in response to DNA ligase I deficiency is conserved in humans, yet the lysine residue that is modified remains to be determined. We propose that PCNA ubiquitylation provides a 'DNA damage code' that allows cells to categorize different types of defects that arise during DNA replication.

Indexed as

Bone NeoplasmsDNA-Binding ProteinsDNA DamageDNA, FungalDNA HelicasesDNA Ligase ATPDNA LigasesDNA RepairGene Expression Regulation, FungalHumansLysineMutationOsteosarcomaProliferating Cell Nuclear AntigenSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCDC9 protein, S cerevisiaeDNA-Binding ProteinsDNA, FungalDNA HelicasesDNA Ligase ATPDNA LigasesLIG1 protein, humanLysineMMS2 protein, S cerevisiaeProliferating Cell Nuclear AntigenRAD18 protein, S cerevisiaeRAD5 protein, S cerevisiaeRAD6 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsUbc4 protein, S cerevisiaeUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID20010813
PMCPMC2799194
OpenAlexW2112841929

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.