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


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Additional Information: Copyright © 2022, Abu-Libdeh et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Uncontrolled Keywords: Breast Neoplasms,DNA Replication,Female,Genetic Predisposition to Disease,Genomic Instability,Humans,Mutation,RecQ Helicases/genetics
Publication ISSN: 1558-8238
Last Modified: 11 Jul 2024 07:23
Date Deposited: 20 Jun 2023 15:10
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Related URLs: https://www.jci ... les/view/147301 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-03-01
Published Online Date: 2022-01-13
Accepted Date: 2022-01-11
Authors: Abu-Libdeh, Bassam
Jhujh, Satpal S
Dhar, Srijita
Sommers, Joshua A
Datta, Arindam
Longo, Gabriel M C
Grange, Laura J
Reynolds, John J (ORCID Profile 0000-0001-8690-5828)
Cooke, Sophie L
McNee, Gavin S
Hollingworth, Robert
Woodward, Beth L
Ganesh, Anil N
Smerdon, Stephen J
Nicolae, Claudia M
Durlacher-Betzer, Karina
Molho-Pessach, Vered
Abu-Libdeh, Abdulsalam
Meiner, Vardiella
Moldovan, George-Lucian
Roukos, Vassilis
Harel, Tamar
Brosh, Robert M
Stewart, Grant S



Version: Published Version

License: Creative Commons Attribution

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