The RECQL4 Protein, Deficient in Rothmund-Thomson Syndrome is Active on Telomeric D-loops Containing DNA Metabolism Blocking Lesions

Overview

Journal DNA Repair (Amst)

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2013 May 21

PMID 23683351

Citations 15

Authors

Leslie K Ferrarelli

Venkateswarlu Popuri

Avik K Ghosh

Takashi Tadokoro

Chandrika Canugovi

Joseph K Hsu

Deborah L Croteau

Vilhelm A Bohr

Affiliations

Soon will be listed here.

Abstract

Telomeres are critical for cell survival and functional integrity. Oxidative DNA damage induces telomeric instability and cellular senescence that are associated with normal aging and segmental premature aging disorders such as Werner Syndrome and Rothmund-Thomson Syndrome, caused by mutations in WRN and RECQL4 helicases respectively. Characterizing the metabolic roles of RECQL4 and WRN in telomere maintenance is crucial in understanding the pathogenesis of their associated disorders. We have previously shown that WRN and RECQL4 display a preference in vitro to unwind telomeric DNA substrates containing the oxidative lesion 8-oxoguanine. Here, we show that RECQL4 helicase has a preferential activity in vitro on telomeric substrates containing thymine glycol, a critical lesion that blocks DNA metabolism, and can be modestly stimulated further on a D-loop structure by TRF2, a telomeric shelterin protein. Unlike that reported for telomeric D-loops containing 8-oxoguanine, RECQL4 does not cooperate with WRN to unwind telomeric D-loops with thymine glycol, suggesting RECQL4 helicase is selective for the type of oxidative lesion. RECQL4's function at the telomere is not yet understood, and our findings suggest a novel role for RECQL4 in the repair of thymine glycol lesions to promote efficient telomeric maintenance.

Citing Articles

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.

Role and Regulation of the RECQL4 Family during Genomic Integrity Maintenance.

Luong T, Bernstein K Genes (Basel). 2021; 12(12).

PMID: 34946868 PMC: 8701316. DOI: 10.3390/genes12121919.

Molecular Mechanisms of the RECQ4 Pathogenic Mutations.

Xu X, Chang C, Li M, Liu C, Liu Y Front Mol Biosci. 2021; 8:791194.

PMID: 34869606 PMC: 8637615. DOI: 10.3389/fmolb.2021.791194.

Comprehensive Synthetic Genetic Array Analysis of Alleles That Interact with Mutation of the RecQ Helicases Hrq1 and Sgs1.

Sanders E, Nguyen P, Rogers C, Bochman M G3 (Bethesda). 2020; 10(12):4359-4368.

PMID: 33115720 PMC: 7718751. DOI: 10.1534/g3.120.401709.

Fanconi anemia-independent DNA inter-strand crosslink repair in eukaryotes.

Rogers C, Simmons Iii R, Fluhler Thornburg G, Buehler N, Bochman M Prog Biophys Mol Biol. 2020; 158:33-46.

PMID: 32877700 PMC: 8201522. DOI: 10.1016/j.pbiomolbio.2020.08.005.

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