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

• DOI: 10.1074/jbc.m111.295063
• Publication Date: 2011-10-29T00:50:17Z
• Authors: Avik K. Ghosh; Marie L. Rossi; Dharmendra Kumar ...; Christopher Dunn; Mahesh Ramamoorthy; Deborah L. Croteau; Yie Liu; Vilhelm A. Bohr
• Keywords: DNA Replication; 0301 basic medicine; Base Sequence; RecQ Helicases; Molecular Sequence Data; Intracellular Signaling Peptides and Proteins; Rothmund-Thomson Syndrome; DNA; Telomere; Protein Transport; 03 medical and health sciences; Exodeoxyribonucleases; Aphidicolin; Gene Knockdown Techniques; Mutation; Humans; Nucleic Acid Conformation; Mutant Proteins; Telomeric Repeat Binding Protein 2; RNA, Small Interfering; Tumor Suppressor p53-Binding Protein 1; HeLa Cells

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.