Inhibition of DNA replication in the 1-cell mouse embryo causes arrest in interphase. In such arrested cells the pattern of protein synthesis progresses as normal through the first cell cycle but does not show the characteristic changes that are associated with mitosis. Synthesis does occur of the 68/70 kd heat shock-like proteins, on the earliest detectable embryonic transcripts synthesised shortly after first cleavage in control embryos. However, the quantitative change in the pattern of protein synthesis, indicative of the major activation of the embryonic genome that normally occurs during G2 of the second cell cycle, is prevented.
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Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFNat Commun
January 2025
Sorbonne Université, CNRS, Laboratory of Computational and Quantitative Biology, LCQB, Paris, France.
Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells.
View Article and Find Full Text PDFNat 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 PDFVirus Res
January 2025
Medical Research Center, Yuebei People's Hospital, Shantou University Medical College, 512025, Shaoguan, China; Shenzhen Immuthy Biotech Co., Ltd, 518107, Shenzhen, Guangdong, China. Electronic address:
Hepatitis B virus (HBV) represents one of the major pathogenic factor that leads to chronic liver diseases and the development of hepatocellular carcinoma (HCC). The currently approved anti-HBV drugs cannot eradicate the virus or block the development of HCC. HBV nucleocapsid consists of the hepatitis B core antigen (HBcAg) and the HBV relaxed-circular partially double-stranded DNA (rcDNA), indispensable in virus replication.
View Article and Find Full Text PDFComput Biol Med
January 2025
Laboratorio de Fisicoquímica Analítica, Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, 54714, Mexico. Electronic address:
Bacterial resistance is a global public health problem because of the ineffectiveness of conventional antibiotics against super pathogens. To counter this situation, the search for or design of new molecules is essential to inhibit the key proteins involved in several stages of bacterial infection. One of these key proteins is DNA gyrase, which is responsible for packaging and unfolding of DNA chains during replication.
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