Background: RecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice.
Results: Here, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment.
Conclusions: Collectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.
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http://dx.doi.org/10.1186/1476-4598-10-83 | DOI Listing |
Microbiol Spectr
December 2023
Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
Biological processes originating from the DNA and RNA can be regulated by the secondary structures present in the stretch of nucleic acids, and the G-quadruplexes are shown to regulate transcription, translation, and replication. In this study, we identified the presence of multiple G-quadruplex sites in the region (oriLyt) of Kaposi's sarcoma-associated herpesvirus (KSHV) DNA, which is essential for DNA replication during the lytic cycle. We demonstrated the roles of these G-quadruplexes through multiple biochemical and biophysical assays in controlling replication and efficient virus production.
View Article and Find Full Text PDFInt J Mol Sci
September 2023
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Base excision repair (BER) corrects forms of oxidative, deamination, alkylation, and abasic single-base damage that appear to have minimal effects on the helix. Since its discovery in 1974, the field has grown in several facets: mechanisms, biology and physiology, understanding deficiencies and human disease, and using BER genes as potential inhibitory targets to develop therapeutics. Within its segregation of short nucleotide (SN-) and long patch (LP-), there are currently six known global mechanisms, with emerging work in transcription- and replication-associated BER.
View Article and Find Full Text PDFNeurobiol Dis
May 2023
DNA Repair Section, National Institute on Aging, Baltimore, MD 21224, USA; Danish Center for Healthy Aging, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address:
Methods Enzymol
August 2022
Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, Washington, DC, United States; National Human Genome Center, College of Medicine, Howard University, Washington, DC, United States. Electronic address:
RecQ helicases participate in a variety of DNA metabolic processes through their multiple biochemical activities. In vitro characterization and cellular studies have suggested that RECQ1 (also known as RECQL or RECQL1) performs its diverse functions through specific interactions with DNA and protein partners. We have taken an unbiased approach to determine the contribution of RECQ1 in genome maintenance and as a putative susceptibility factor in breast cancer.
View Article and Find Full Text PDFFront Mol Biosci
June 2022
Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA, United States.
Named the "caretakers" of the genome, RecQ helicases function in several pathways to maintain genomic stability and repair DNA. This highly conserved family of enzymes consist of five different proteins in humans: RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic germline mutations in , , and have been linked to rare cancer-predisposing syndromes.
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