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RecQ helicases are known as "caretakers" of the genome for their conserved helicase activities to resolve different complex DNA structures. Aberrant accumulation of unsolved DNA structures could lead to defects in DNA replication, gene transcription, and unrepaired DNA lesions. Pathogenic mutations on , , and are associated with several pathological conditions, namely Bloom syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson syndrome (RTS). These syndromes are characterized by genomic instability and cancer predisposition. Additionally, some RecQ helicase diseases are linked to developmental defects and premature aging. In this review, we provide an overview of the RecQ helicases, focusing on the molecular functions and mechanisms, as well as the consequences of their dysfunction in cellular processes. We also discuss the significance of RecQ helicases in preventing various genetic disorders (BS, WS, RTS) and the insights obtained from the different animal models developed for studying the pathophysiology of RecQ helicase deficiencies.
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http://dx.doi.org/10.18632/aging.206291 | DOI Listing |
Nucleic Acids Res
August 2025
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Rad51 and meiosis-specific Dmc1 catalyze homologous recombination (HR) between maternal and paternal chromosomes during meiosis in many sexual eukaryotes, generating three interhomolog (IH) recombination products: non-crossovers (NCOs), class I interference-sensitive crossovers (COs), and class II non-interfering COs. CO interference suppresses relatively close CO formation. Some COs form chiasmata, which physically connect homologous chromosomes and ensure proper chromosome segregation during meiosis I.
View Article and Find Full Text PDFElife
September 2025
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, United States.
Y-family DNA polymerases (Pols) are intrinsically highly error-prone; yet they conduct predominantly error-free translesion synthesis (TLS) in normal human cells. In response to DNA damage, Y-family Pols assemble and function together with WRN, WRNIP1, and Rev1 in TLS. Among these proteins, WRN possesses a 3'→5' exonuclease activity and an ATPase/3'→5' DNA helicase activity, and WRNIP1 has a DNA-dependent ATPase activity.
View Article and Find Full Text PDFJ Cell Biol
October 2025
Department of Biology, Carnegie Mellon University, Pittsburgh, PA, USA.
Many cancers use an alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT telomeric DNA synthesis occurs in ALT-associated PML bodies (APBs). However, the mechanisms by which APBs form are not well understood.
View Article and Find Full Text PDFMethods Mol Biol
August 2025
Center for Education in Laboratory Animal Research, Chubu University, Kasugai, Aichi, Japan.
Complex chromosomal rearrangements (CCRs) present significant challenges and opportunities in cancer and congenital disease research. Reproducing these rearrangements experimentally in animal models has been challenging, limiting our insights into their mechanisms and impacts. Recql5 is a critical DNA helicase that participates in replication, transcription, and repair processes.
View Article and Find Full Text PDFNat Commun
August 2025
Center for Chromosome Stability, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Mitotic DNA synthesis (MiDAS) serves to complete the replication of genomic loci that are not fully replicated in S phase in response to replication stress. Previous studies suggest that MiDAS might proceed via break-induced DNA replication, a sub-pathway of homologous recombination repair activated at broken or collapsed replication forks. We set out to define whether DNA double strand break end-resection factors play a role in MiDAS.
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