Evidence map›Paper›PMID 33406258›Full record

ArticleNucleic acids research2021

SUMOylation mediates CtIP's functions in DNA end resection and replication fork protection.

Andrew J Locke, Lazina Hossain, Glynnis McCrostie, Daryl A Ronato, Amira Fitieh, Tanzeem Ahmed Rafique, Fatemeh Mashayekhi, Mobina Motamedi, Jean-Yves Masson, Ismail Hassan Ismail

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. SUMO and the DNA damage response.Biochemical Society transactions · 2024
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Advances in SUMO-based regulation of homologous recombination.Current opinion in genetics & development · 2021
    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

10 authors at 3 institutions in 2 countries.

Andrew J LockeDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Lazina HossainDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Glynnis McCrostieDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Daryl A RonatoOncology Division, CHU de Québec-Université Laval Research Center, Québec City, Québec, G1R 3S3, Canada.
Amira FitiehDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Tanzeem Ahmed RafiqueDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Fatemeh MashayekhiDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Mobina MotamediDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
Jean-Yves MassonOncology Division, CHU de Québec-Université Laval Research Center, Québec City, Québec, G1R 3S3, Canada.
Ismail Hassan IsmailDivision of Experimental Oncology, Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta; Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada.
University of Alberta · CACairo University · EGUniversité Laval · CA

Funding

CIHR FDN-388879CIHR MOP-365197
6 · The paper itself

Abstract

Double-strand breaks and stalled replication forks are a significant threat to genomic stability that can lead to chromosomal rearrangements or cell death. The protein CtIP promotes DNA end resection, an early step in homologous recombination repair, and has been found to protect perturbed forks from excessive nucleolytic degradation. However, it remains unknown how CtIP's function in fork protection is regulated. Here, we show that CtIP recruitment to sites of DNA damage and replication stress is impaired upon global inhibition of SUMOylation. We demonstrate that CtIP is a target for modification by SUMO-2 and that this occurs constitutively during S phase. The modification is dependent on the activities of cyclin-dependent kinases and the PI-3-kinase-related kinase ATR on CtIP's carboxyl-terminal region, an interaction with the replication factor PCNA, and the E3 SUMO ligase PIAS4. We also identify residue K578 as a key residue that contributes to CtIP SUMOylation. Functionally, a CtIP mutant where K578 is substituted with a non-SUMOylatable arginine residue is defective in promoting DNA end resection, homologous recombination, and in protecting stalled replication forks from excessive nucleolytic degradation. Our results shed further light on the tightly coordinated regulation of CtIP by SUMOylation in the maintenance of genome stability.

Indexed as

DNA ReplicationProtein Processing, Post-TranslationalSumoylationAmino Acid SubstitutionArginineAtaxia Telangiectasia Mutated ProteinsCell LineCyclin-Dependent KinasesDNA Breaks, Double-StrandedDNA End-Joining RepairEndodeoxyribonucleasesGenes, ReporterGenomic InstabilityHumansLysinePoly-ADP-Ribose Binding ProteinsArginineAtaxia Telangiectasia Mutated ProteinsATR protein, humanCyclin-Dependent KinasesEndodeoxyribonucleasesLysinePCNA protein, humanPIAS4 protein, humanPoly-ADP-Ribose Binding ProteinsProliferating Cell Nuclear AntigenProtein Inhibitors of Activated STATRBBP8 protein, humanRecombinant Fusion ProteinsRNA, Small Interfering

Identifiers

PMID33406258
PMCPMC7826263
OpenAlexW3118332071

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.