Nuclear eukaryotic genomes are transcribed by three related RNA polymerases (Pol), which transcribe distinct gene sets. Specific Pol recruitment is achieved through selective core promoter recognition by basal transcription factors (TFs). Transcription by an inappropriate Pol appears to be rare and to generate mostly unstable products. A collection of short noncoding RNA genes [for example, small nuclear RNA (snRNA) or 7SK RNA genes], which play essential roles in processes such as maturation of RNA molecules or control of Pol II transcription elongation, possess highly similar core promoters, and yet are transcribed for some by Pol II and for others by Pol III as a result of small promoter differences. Here we discuss the mechanisms of selective Pol recruitment to such promoters.
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http://dx.doi.org/10.1016/j.tig.2019.04.001 | DOI Listing |
Nat Commun
January 2025
Robson DNA Science Centre, Charbonneau Cancer Institute, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
View Article and Find Full Text PDFThe replicative polymerase delta is inefficient copying repetitive DNA sequences. Error-prone translesion polymerases have been shown to switch with high-fidelity replicative polymerases to help navigate repetitive DNA. We and others have demonstrated the importance of one such translesion polymerase, polymerase Eta (pol eta), in facilitating replication at genomic regions called common fragile sites (CFS), which are difficult-to-replicate genomic regions that are hypersensitive to replication stress.
View Article and Find Full Text PDFJ Biol Chem
January 2025
State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. Electronic address:
Melanoma differentiation-associated gene 5 (MDA5) initiates type I interferon (IFN) production by detecting cytosolic viral RNA. Mammalian MDA5 is an IFN-inducible gene and controlled by IFN regulatory factor 1 (IRF1). Teleost MDA5 also induces type I IFN production in response to viruses, yet its regulation remains largely unexplored.
View Article and Find Full Text PDFCureus
December 2024
Department of Physiotherapy, Institute of Physiotherapy and Health Sciences, The Jerzy Kukuczka Academy of Physical Education, Katowice, POL.
Introduction: Anterior cruciate ligament (ACL) reconstruction (ACLR) is the gold standard for treating ACL injuries, particularly in soccer players who are at a high risk of knee injury. While professional athletes often return to sport (RTS) within 7-10 months after ACLR, non-elite players experience significant delays. There is a need to investigate neuromuscular deficits and functional asymmetries in the non-elite group, which may persist even after clearance for RTS.
View Article and Find Full Text PDFAIDS Behav
January 2025
Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, USA.
Military members and female sex workers (FSWs) may be more likely to acquire or transmit HIV. Mapping HIV transmission across these high-risk populations and identifying behaviors associated with sexual network clustering are needed for effective HIV prevention approaches. A cross-sectional study recruited participants newly diagnosed with HIV among militaries, civilians, and FSWs in Zambia, Senegal, and Democratic Republic of the Congo (DRC).
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