Evidence map›Paper›PMID 22456510›Full record

ArticleMolecular biology of the cell2012

c-Jun N-terminal kinase-mediated Rad18 phosphorylation facilitates Polη recruitment to stalled replication forks.

Laura R Barkley, Komaraiah Palle, Michael Durando, Tovah A Day, Aditi Gurkar, Naoko Kakusho, Jianying Li, Hisao Masai, Cyrus Vaziri

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2012. 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
0.9field-weighted citation impact, top 26% 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, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Translesion DNA polymerases in eukaryotes: what makes them tick?Critical reviews in biochemistry and molecular biology · 2017
    Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. UnCHKed DNA replication: A stressful matter.Cell cycle (Georgetown, Tex.) · 2012
    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

9 authors at 6 institutions in 3 countries.

Laura R BarkleyNational Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
Komaraiah Palle
Michael Durando
Tovah A Day
Aditi Gurkar
Naoko Kakusho
Jianying Li
Hisao Masai
Cyrus Vaziri
University of North Carolina at Chapel Hill · USTokyo Metropolitan Institute of Medical Science · JPDana-Farber Cancer Institute · USDuke University · USHarvard University · USOllscoil na Gaillimhe – University of Galway · IE

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
A Novel Carcinogen-Induced Cell Cycle CheckpointR01ES009558 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAZIRI, CYRUS · 2002 to 2016
$4.8M
A Novel Role for the Fanconi Anemia Pathway in Replication of B[a]P-Adducted DNAR01ES016280 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAZIRI, CYRUS · 2008 to 2012
$1.5M
NOVEL CARCINOGEN INDUCED CELL CYCLE CHECKPOINTR29ES009558 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI VAZIRI, CYRUS · 1998 to 2001
$221k
Regulatory Signaling in Repair of Environmentally Induced DNA DamageF30ES019449 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DURANDO, MICHAEL LUCA · 2010 to 2014
$155k
NCI NIH HHS P30 CA016086NIEHS NIH HHS ES016280NIEHS NIH HHS ES09558NIEHS NIH HHS F30 ES019449NIEHS NIH HHS R01 ES009558NIEHS NIH HHS R01 ES016280NIEHS NIH HHS R29 ES009558
6 · The paper itself

Abstract

The E3 ubiquitin ligase Rad18 chaperones DNA polymerase η (Polη) to sites of UV-induced DNA damage and monoubiquitinates proliferating cell nuclear antigen (PCNA), facilitating engagement of Polη with stalled replication forks and promoting translesion synthesis (TLS). It is unclear how Rad18 activities are coordinated with other elements of the DNA damage response. We show here that Ser-409 residing in the Polη-binding motif of Rad18 is phosphorylated in a checkpoint kinase 1-dependent manner in genotoxin-treated cells. Recombinant Rad18 was phosphorylated specifically at S409 by c-Jun N-terminal kinase (JNK) in vitro. In UV-treated cells, Rad18 S409 phosphorylation was inhibited by a pharmacological JNK inhibitor. Conversely, ectopic expression of JNK and its upstream kinase mitogen-activated protein kinase kinase 4 led to DNA damage-independent Rad18 S409 phosphorylation. These results identify Rad18 as a novel JNK substrate. A Rad18 mutant harboring a Ser → Ala substitution at S409 was compromised for Polη association and did not redistribute Polη to nuclear foci or promote Polη-PCNA interaction efficiently relative to wild-type Rad18. Rad18 S409A also failed to fully complement the UV sensitivity of Rad18-depleted cells. Taken together, these results show that Rad18 phosphorylation by JNK represents a novel mechanism for promoting TLS and DNA damage tolerance.

Indexed as

DNA ReplicationProtein Processing, Post-TranslationalAmino Acid MotifsCell Line, TumorDNA-Binding ProteinsDNA DamageDNA-Directed DNA PolymeraseHumansJNK Mitogen-Activated Protein KinasesMolecular Sequence DataPhosphorylationProliferating Cell Nuclear AntigenProtein BindingProtein Interaction Domains and MotifsProtein TransportSerineDNA-Binding ProteinsDNA-Directed DNA PolymeraseJNK Mitogen-Activated Protein KinasesPOLK protein, humanProliferating Cell Nuclear AntigenRAD18 protein, humanRad30 proteinSerineUBE2A protein, humanUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesY-Family DNA Polymerases

Identifiers

PMID22456510
PMCPMC3350557
OpenAlexW2100500716

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.