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DNA replication is tightly regulated to ensure genomic stability and prevent several diseases, including cancers. Eukaryotes and archaea partly achieve this regulation by strictly controlling the activation of hexameric minichromosome maintenance (MCM) helicase rings that unwind DNA during its replication. In eukaryotes, MCM activation critically relies on the sequential recruitment of the essential factors Cdc45 and a tetrameric GINS complex at the onset of the S-phase to generate a larger CMG complex. We present the crystal structure of the tetrameric GINS complex from the archaeal organism Saccharolobus solfataricus (Sso) to reveal a core structure that is highly similar to the previously determined GINS core structures of other eukaryotes and archaea. Using molecular modeling, we illustrate that a subdomain of SsoGINS would need to move to accommodate known interactions of the archaeal GINS complex and to generate a SsoCMG complex analogous to that of eukaryotes.
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http://dx.doi.org/10.1107/S2053230X25003085 | DOI Listing |
Elife
September 2025
Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
DNA replication requires recruitment of Cdc45 and GINS into the MCM double hexamer by initiation factors to form an active helicase, the Cdc45-MCM-GINS (CMG) complex, at the replication origins. The initiation factor Sld3 is a central regulator of Cdc45 and GINS recruitment, working with Sld7 together. However, the mechanism through which Sld3 regulates CMG complex formation remains unclear.
View Article and Find Full Text PDFPhys Rev Lett
June 2025
Université Paris-Saclay, IJCLab, Université Paris-Sud, Orsay, France.
We employed laser spectroscopy of atomic transitions to measure the nuclear charge radii and electromagnetic properties of the high-spin isomeric states in neutron-rich indium isotopes (Z=49) near the closed proton and neutron shells at Z=50 and N=82. Our data reveal a reduction in the nuclear charge radius and intrinsic quadrupole moment when protons and neutrons are fully aligned in ^{129}In(N=80), to form the high spin isomer. Such a reduction is not observed in ^{127}In(N=78), where more complex configurations can be formed by the existence of four neutron holes.
View Article and Find Full Text PDFInt J Parasitol
July 2025
University of Liverpool, Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, Leahurst Main Building, Neston, Cheshire CH64 7TE, England, UK. Electronic address:
Gastrointestinal nematode (GIN) parasite infections in grazing livestock cause significant disease, and are responsible for estimated annual losses of over €1.8 billion in Europe alone. The management of GINs in cattle is threatened by anthelmintic drug resistance (AR).
View Article and Find Full Text PDFGenetics
September 2025
Department of Biology and Biotechnology "C. Darwin", Sapienza University of Rome, Rome 00185, Italy.
The CMG (Cdc45-MCM-GINS) complex is a conserved helicase that plays an essential DNA unwinding function at replication forks. Here, we analyzed the mitotic phenotypes caused in Drosophila by knockdown of Cdc45, Mcm5, and the four GINS genes (Sld5, Psf1, Psf2, and Psf3). Silencing of these genes resulted in virtually identical mitotic phenotypes.
View Article and Find Full Text PDFExp Hematol Oncol
May 2025
Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, 92354, CA, USA.
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year overall survival (OS) rate of approximately 12%. More than 90% of PDAC patients harbor oncogenic mutations in the Kirsten rat sarcoma viral homolog (KRAS) gene. MRTX1133 (MRTX), a novel inhibitor of KRAS (the most common KRAS mutation found in pancreatic and colon cancers) has shown promise as a therapeutic agent.
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