Evidence map›Paper›PMID 18776215›Full record

ArticleNucleic acids research2008

Evidence for an inositol hexakisphosphate-dependent role for Ku in mammalian nonhomologous end joining that is independent of its role in the DNA-dependent protein kinase.

Joyce C Y Cheung, Brenda Salerno, Les A Hanakahi

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. The Multifaceted Roles of Ku70/80.International journal of molecular sciences · 2021
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. The flexible and iterative steps within the NHEJ pathway.Progress in biophysics and molecular biology
    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

3 authors at 1 institution in 1 country.

Joyce C Y CheungDepartment of Biochemistry and Molecular Biology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Brenda Salerno
Les A Hanakahi
Johns Hopkins University · US

Funding

SCREENING OF CELLS &TISSUES FOR HIVU42RR005991 · NCRR · BIOVEST INTERNATIONAL, INC. · PI HIRSCHEL, MARK D. · 1992 to 2005
$3.0M
MOLECULAR MECHANISMS OF NHEJ IN MAMMALIAN CELLSR01GM070639 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HANAKAHI, LESLYN A · 2004 to 2008
$1.2M
Minority Predoctoral Fellowship ProgramF31GM072114 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI SALERNO, BRENDA · 2004 to 2006
$131k
NCRR NIH HHS U42 RR05991NIGMS NIH HHS F31 GM072114NIGMS NIH HHS GM00639NIGMS NIH HHS GM070639NIGMS NIH HHS GM072114NIGMS NIH HHS R01 GM070639
6 · The paper itself

Abstract

Nonhomologous end-joining (NHEJ) is an important pathway for the repair of DNA double-strand breaks (DSBs) and plays a critical role in maintaining genomic stability in mammalian cells. While Ku70/80 (Ku) functions in NHEJ as part of the DNA-dependent protein kinase (DNA-PK), genetic evidence indicates that the role of Ku in NHEJ goes beyond its participation in DNA-PK. Inositol hexakisphosphate (IP(6)) was previously found to stimulate NHEJ in vitro and Ku was identified as an IP(6)-binding factor. Through mutational analysis, we identified a bipartite IP(6)-binding site in Ku and generated IP(6)-binding mutants that ranged from 1.22% to 58.48% of wild-type binding. Significantly, these Ku IP(6)-binding mutants were impaired for participation in NHEJ in vitro and we observed a positive correlation between IP(6) binding and NHEJ. Ku IP(6)-binding mutants were separation-of-function mutants that bound DNA and activated DNA-PK as well as wild-type Ku. Our observations identify a hitherto undefined IP(6)-binding site in Ku and show that this interaction is important for DSB repair by NHEJ in vitro. Moreover, these data indicate that in addition to binding of exposed DNA termini and activation of DNA-PK, the Ku heterodimer plays a role in mammalian NHEJ that is regulated by binding of IP(6).

Indexed as

DNA RepairAntigens, NuclearBinding SitesDNA-Activated Protein KinaseDNA-Binding ProteinsHeLa CellsHumansKu AutoantigenMutationPhytic AcidProtein BindingProtein SubunitsAntigens, NuclearDNA-Activated Protein KinaseDNA-Binding ProteinsKu AutoantigenPhytic AcidProtein SubunitsXrcc6 protein, human

Identifiers

PMID18776215
PMCPMC2553570
OpenAlexW2164410997

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.