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As well as accurately duplicating DNA, the eukaryotic replisome performs a variety of other crucial tasks to maintain genomic stability. For example, organizational elements, like cohesin, must be transferred from the front of the fork to the new strands, and when there is replication stress, forks need to be protected and checkpoint signalling activated. The Tof1-Csm3 (or Timeless-Tipin in humans) Fork Protection Complex (FPC) ensures efficient replisome progression and is required for a range of replication-associated activities. Recent studies have begun to reveal the structure of this complex, and how it functions within the replisome to perform its diverse roles. The core of the FPC acts as a DNA grip on the front of the replisome to regulate fork progression. Other flexibly linked domains and motifs mediate interactions with proteins and specific DNA structures, enabling the FPC to act as a hub at the head of the replication fork.
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http://dx.doi.org/10.1007/978-3-031-00793-4_3 | DOI Listing |
Sci Adv
August 2025
Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, 11560 University Avenue, Edmonton T6G 1Z2, Alberta, Canada.
Replication stress (RS) poses a threat to genome stability and drives genomic rearrangements. The homologous recombination (HR) pathway repairs stalled replication forks (RFs) and prevents such instability. Through an E3 ubiquitin ligase screen aimed at identifying regulators of RAD51, we identified macrophage erythroblast attacher (MAEA), a core component of C-terminal to Lish (CTLH) E3 ubiquitin ligase complex, as a regulator of the HR pathway.
View Article and Find Full Text PDFACS Sens
August 2025
The McComish Department of Electrical Engineering and Computer Science, Jerome J. Lohr College of Engineering, South Dakota State University, Brookings, South Dakota 57007, United States.
Plants emit volatile organic compounds (VOCs) in response to biotic and abiotic stress, serving as early indicators of health. Among them, ()-2-Hexenal─a key green leaf volatile (GLV)─signals stress from pathogen infection or herbivory. Real-time detection of ()-2-hexenal at trace levels is crucial for early diagnosis, crop protection, and environmental sustainability.
View Article and Find Full Text PDFPhotoacoustics
October 2025
International Cooperation Joint Laboratory for Optoelectronic Hybrid Integrated Circuits, Jinan University, Guangzhou 510632, China.
Accurate and rapid detection of hydrogen and hydrocarbons is critical for safety and efficiency in modern energy, industrial, and environmental systems. However, selective and simultaneous quantification of these species remains a significant technical challenge. Here, we introduce conductance-photoacoustic spectroscopy (ConPAS), an integrated sensing approach that combines conductance-based resonance modulation with quartz-enhanced photoacoustic spectroscopy in a single device.
View Article and Find Full Text PDFNat Commun
August 2025
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
The DNA damage response (DDR) mechanisms that allow cells to tolerate DNA replication stress are critically important for genome stability and cell viability. Using an unbiased genetic screen, we identify a role for the RING finger E3 ubiquitin ligase RNF25 in promoting DNA replication stress tolerance. In response to DNA replication stress, RNF25-deficient cells generate aberrantly high levels of single-stranded DNA (ssDNA), accumulate in S-phase and show reduced mitotic entry.
View Article and Find Full Text PDFDNA Repair (Amst)
August 2025
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
Maintaining genome stability during DNA replication is a critical cellular challenge. Various surveillance and repair mechanisms have evolved to cope with replication stress, which can be caused by environmental insults, metabolic byproducts, complex DNA structures in the genome, and replication-transcription conflicts. This perspective highlights a newly identified cytosolic DNA/Ca-dependent signaling pathway that plays a crucial role in protecting stalled replication forks.
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