Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1
Bassam Abu-Libdeh, … , Robert M. Brosh Jr., Grant S. Stewart
Bassam Abu-Libdeh, … , Robert M. Brosh Jr., Grant S. Stewart
Published January 13, 2022
Citation Information: J Clin Invest. 2022;132(5):e147301. https://doi.org/10.1172/JCI147301.
View: Text | PDF
Research Article Cell biology Genetics

RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1

  • Text
  • PDF
Abstract

Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene. The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity and were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser), located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase, and fork restoration activity, while its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder.

Authors

Bassam Abu-Libdeh, Satpal S. Jhujh, Srijita Dhar, Joshua A. Sommers, Arindam Datta, Gabriel M.C. Longo, Laura J. Grange, John J. Reynolds, Sophie L. Cooke, Gavin S. McNee, Robert Hollingworth, Beth L. Woodward, Anil N. Ganesh, Stephen J. Smerdon, Claudia M. Nicolae, Karina Durlacher-Betzer, Vered Molho-Pessach, Abdulsalam Abu-Libdeh, Vardiella Meiner, George-Lucian Moldovan, Vassilis Roukos, Tamar Harel, Robert M. Brosh Jr., Grant S. Stewart

×

Figure 5

Cells from a patient with RECON syndrome display a reduced efficiency of replication in the presence of TOP1/2 inhibitors.

Options: View larger image (or click on image) Download as PowerPoint
Cells from a patient with RECON syndrome display a reduced efficiency of...
(A) LCLs and (B) complemented RECQL1-P1-1 patient fibroblasts were sequentially labeled with CldU (red) and IdU (green) as shown. Stalled forks (red-only tracks) were quantified. The mean of 4 independent experiments is shown. A minimum of 200 forks were counted per condition. #P < 0.05 and ##P < 0.01, by 1-way ANOVA with Tukey’s multiple-comparison test. (C) LCLs and (D) complemented fibroblasts were sequentially labeled with CldU and IdU (with or without 50 nM CPT or ETOP) as shown. The length of the CldU and IdU tracks of dual-labeled DNA fibers (>150 per condition) was measured, and the ratio of IdU/CldU track length was calculated, which represents the efficiency of replication in the presence or absence of CPT or ETOP. The median of 3 independent experiments is shown (red line). ###P < 0.001, by Kruskal-Wallis test with Dunn’s multiple comparison.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts