RECQL4, the Protein Mutated in Rothmund-Thomson Syndrome, Functions in Telomere Maintenance

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Nov 1

PMID 22039056

Citations 67

Authors

Avik K Ghosh

Marie L Rossi

Dharmendra Kumar Singh

Christopher Dunn

Mahesh Ramamoorthy

Deborah L Croteau

Yie Liu

Vilhelm A Bohr

Affiliations

Soon will be listed here.

Abstract

Telomeres are structures at the ends of chromosomes and are composed of long tracks of short tandem repeat DNA sequences bound by a unique set of proteins (shelterin). Telomeric DNA is believed to form G-quadruplex and D-loop structures, which presents a challenge to the DNA replication and repair machinery. Although the RecQ helicases WRN and BLM are implicated in the resolution of telomeric secondary structures, very little is known about RECQL4, the RecQ helicase mutated in Rothmund-Thomson syndrome (RTS). Here, we report that RTS patient cells have elevated levels of fragile telomeric ends and that RECQL4-depleted human cells accumulate fragile sites, sister chromosome exchanges, and double strand breaks at telomeric sites. Further, RECQL4 localizes to telomeres and associates with shelterin proteins TRF1 and TRF2. Using recombinant proteins we showed that RECQL4 resolves telomeric D-loop structures with the help of shelterin proteins TRF1, TRF2, and POT1. We also found a novel functional synergistic interaction of this protein with WRN during D-loop unwinding. These data implicate RECQL4 in telomere maintenance.

Citing Articles

RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome.

Ashraf R, Polasek-Sedlackova H, Marini V, Prochazkova J, Hasanova Z, Zacpalova M Nat Commun. 2025; 16(1):1302.

PMID: 39900600 PMC: 11791078. DOI: 10.1038/s41467-025-56518-1.

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Mackay H, Stone H, Ronson G, Ellis K, Lanz A, Aghabi Y Nat Commun. 2024; 15(1):8102.

PMID: 39284827 PMC: 11405836. DOI: 10.1038/s41467-024-52250-4.

Interdependence between Nuclear Pore Gatekeepers and Genome Caretakers: Cues from Genome Instability Syndromes.

Larizza L, Colombo E Int J Mol Sci. 2024; 25(17).

PMID: 39273335 PMC: 11394955. DOI: 10.3390/ijms25179387.

Rothmund-Thomson syndrome, a disorder far from solved.

Martins D, di Lazzaro Filho R, Bertola D, Hoch N Front Aging. 2023; 4:1296409.

PMID: 38021400 PMC: 10676203. DOI: 10.3389/fragi.2023.1296409.

Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase.

Papageorgiou A, Pospisilova M, Cibulka J, Ashraf R, Waudby C, Kaderavek P Nat Commun. 2023; 14(1):6751.

PMID: 37875529 PMC: 10598209. DOI: 10.1038/s41467-023-42503-z.

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