Evidence map›Paper›PMID 28325877›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Dual-utility NLS drives RNF169-dependent DNA damage responses.

Liwei An, Yiyang Jiang, Howin H W Ng, Ellen P S Man, Jie Chen, Ui-Soon Khoo, Qingguo Gong, Michael S Y Huen

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Liwei AnSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Yiyang JiangSchool of Life Sciences, University of Science and Technology of China, Hefei, China.
Howin H W NgSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Ellen P S ManDepartment of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Jie ChenSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Ui-Soon KhooDepartment of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; huen.michael@hku.hk uskhoo@pathology.hku.hk qgg@ustc.edu.cn.
Qingguo GongSchool of Life Sciences, University of Science and Technology of China, Hefei, China; huen.michael@hku.hk uskhoo@pathology.hku.hk qgg@ustc.edu.cn.
Michael S Y HuenSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; huen.michael@hku.hk uskhoo@pathology.hku.hk qgg@ustc.edu.cn.
University of Hong Kong · HKUniversity of Science and Technology of China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Loading of p53-binding protein 1 (53BP1) and receptor-associated protein 80 (RAP80) at DNA double-strand breaks (DSBs) drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA repair. ring finger protein 169 (RNF169) maintains the balance by limiting the deposition of DNA damage mediator proteins at the damaged chromatin. We report here that this attribute is accomplished, in part, by a predicted nuclear localization signal (NLS) that not only shuttles RNF169 into the nucleus but also promotes its stability by mediating a direct interaction with the ubiquitin-specific protease USP7. Guided by the crystal structure of USP7 in complex with the RNF169 NLS, we uncoupled USP7 binding from its nuclear import function and showed that perturbing the USP7-RNF169 complex destabilized RNF169, compromised high-fidelity DSB repair, and hypersensitized cells to poly (ADP-ribose) polymerase inhibition. Finally, expression of USP7 and RNF169 positively correlated in breast cancer specimens. Collectively, our findings uncover an NLS-mediated bipartite mechanism that supports the nuclear function of a DSB response protein.

Indexed as

AdultAgedAged, 80 and overBreast NeoplasmsCell LineCrystallography, X-RayDNA DamageDNA RepairFemaleHumansMiddle AgedNuclear Localization SignalsProtein ConformationProtein DomainsUbiquitinationUbiquitin-Protein LigasesNuclear Localization SignalsRNF169 protein, humanUbiquitin-Protein LigasesUbiquitin-Specific Peptidase 7USP7 protein, humandeubiquitylationDNA damageDNA repairRNF169USP7

Identifiers

PMID28325877
PMCPMC5389323
OpenAlexW2589286460

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.