Evidence map›Paper›PMID 29788478›Full record

ArticleNucleic acids research2018

A minimal threshold of FANCJ helicase activity is required for its response to replication stress or double-strand break repair.

Sanjay Kumar Bharti, Joshua A Sommers, Sanket Awate, Marina A Bellani, Irfan Khan, Lynda Bradley, Graeme A King, Yeonee Seol, Venkatasubramanian Vidhyasagar, Yuliang Wu and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. 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
1.5field-weighted citation impact, top 18% 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, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022
    Article
  8. Article
  9. Article
  10. Helicase-inactivatingCold Spring Harbor molecular case studies · 2020
    Article
  11. Article
  12. Review
  13. RareCancer research · 2020
    Article
  14. Fundamentals of G-quadruplex biology.Annual reports in medicinal chemistry · 2020
    Article
  15. Review
  16. Review
  17. 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

18 authors at 7 institutions in 4 countries.

Sanjay Kumar BhartiLaboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Joshua A SommersLaboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Sanket AwateLaboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Marina A BellaniLaboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Irfan KhanLaboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Lynda BradleyLaboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Graeme A KingLaboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yeonee SeolLaboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Venkatasubramanian VidhyasagarDepartment of Biochemistry, University of Saskatchewan, Health Sciences Building, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
Yuliang WuDepartment of Biochemistry, University of Saskatchewan, Health Sciences Building, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
Takuye AbeIFOM, the FIRC Institute for Molecular Oncology Foundation, Milan, Italy.
Koji KobayashiIFOM, the FIRC Institute for Molecular Oncology Foundation, Milan, Italy.
Kazuo Shin-YaDepartment of Life Science and Biotechnology Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST) 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
Hiroyuki KitaoDepartment of Molecular Cancer Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Marc S WoldDepartment of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Dana BranzeiIFOM, the FIRC Institute for Molecular Oncology Foundation, Milan, Italy.
Keir C NeumanLaboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Robert M BroshLaboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA.
National Institute on Aging · USNational Institutes of Health · USIFOM · ITSaskatchewan Health · CAKyushu University · JPNational Institute of Advanced Industrial Science and Technology · JPUniversity of Iowa · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
Single-molecule measurements of DNA topology and topoisomerasesZIAHL001056 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI NEUMAN, KEIR · 2009 to 2025
$22.6M
Roles Of DNA Helicases In Pathways Required For Maintenance Of Genomic StabilityZIAAG000741 · NIA · NATIONAL INSTITUTE ON AGING · PI BROSH, ROBERT · 2009 to 2025
$7.6M
Model Genetic Systems to Study DNA RepairZIAAG000752 · NIA · NATIONAL INSTITUTE ON AGING · PI BROSH, ROBERT · 2009 to 2025
$4.8M
Fanconi Anemia PathwayZIAAG000753 · NIA · NATIONAL INSTITUTE ON AGING · PI BROSH, ROBERT · 2009 to 2025
$4.3M
6 · The paper itself

Abstract

Fanconi Anemia (FA) is characterized by bone marrow failure, congenital abnormalities, and cancer. Of over 20 FA-linked genes, FANCJ uniquely encodes a DNA helicase and mutations are also associated with breast and ovarian cancer. fancj-/- cells are sensitive to DNA interstrand cross-linking (ICL) and replication fork stalling drugs. We delineated the molecular defects of two FA patient-derived FANCJ helicase domain mutations. FANCJ-R707C was compromised in dimerization and helicase processivity, whereas DNA unwinding by FANCJ-H396D was barely detectable. DNA binding and ATP hydrolysis was defective for both FANCJ-R707C and FANCJ-H396D, the latter showing greater reduction. Expression of FANCJ-R707C or FANCJ-H396D in fancj-/- cells failed to rescue cisplatin or mitomycin sensitivity. Live-cell imaging demonstrated a significantly compromised recruitment of FANCJ-R707C to laser-induced DNA damage. However, FANCJ-R707C expressed in fancj-/- cells conferred resistance to the DNA polymerase inhibitor aphidicolin, G-quadruplex ligand telomestatin, or DNA strand-breaker bleomycin, whereas FANCJ-H396D failed. Thus, a minimal threshold of FANCJ catalytic activity is required to overcome replication stress induced by aphidicolin or telomestatin, or to repair bleomycin-induced DNA breakage. These findings have implications for therapeutic strategies relying on DNA cross-link sensitivity or heightened replication stress characteristic of cancer cells.

Indexed as

DNA Breaks, Double-StrandedDNA RepairDNA ReplicationAdenosine TriphosphatasesAnimalsAphidicolinCell LineCheckpoint Kinase 1ChickensCisplatinDNA HelicasesDNA, Single-StrandedFanconi AnemiaFanconi Anemia Complementation Group ProteinsG-QuadruplexesMutation, MissenseAdenosine TriphosphatasesAphidicolinBRIP1 protein, humanCheckpoint Kinase 1CisplatinDNA HelicasesDNA, Single-StrandedFanconi Anemia Complementation Group ProteinsOxazolesRad51 RecombinaseRecombinasesReplication Protein ARNA Helicasestelomestatin

Identifiers

PMID29788478
PMCPMC6159516
OpenAlexW2803673476

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.