RecQ helicase expression in patients with telomeropathies.

Mol Biol Rep

Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - 7 o andar, sala 743 - HCRP, Ribeirão Preto, SP, 14049-900, Brazil.

Published: June 2024

Background: Telomeropathies are a group of inherited disorders caused by germline pathogenic variants in genes involved in telomere maintenance, resulting in excessive telomere attrition that affects several tissues, including hematopoiesis. RecQ and RTEL1 helicases contribute to telomere maintenance by unwinding telomeric structures such as G-quadruplexes (G4), preventing replication defects. Germline RTEL1 variants also are etiologic in telomeropathies.

Methods And Results: Here we investigated the expression of RecQ (RECQL1, BLM, WRN, RECQL4, and RECQL5) and RTEL1 helicase genes in peripheral blood mononuclear cells (PBMCs) from human telomeropathy patients. The mRNA expression levels of all RecQ helicases, but not RTEL1, were significantly downregulated in patients' primary cells. Reduced RecQ expression was not attributable to cell proliferative exhaustion, as RecQ helicases were not attenuated in T cells exhausted in vitro. An additional fifteen genes involved in DNA damage repair and RecQ functional partners also were downregulated in the telomeropathy cells.

Conclusion: These findings indicate that the expression of RecQ helicases and functional partners involved in DNA repair is downregulated in PBMCs of telomeropathy patients.

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http://dx.doi.org/10.1007/s11033-024-09678-0DOI Listing

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