Fission yeast Cid12 is a member of the Cid1 family of specialized poly(A) polymerases. Like cells lacking cid1, cid12Delta mutants were shown to have checkpoint defects when DNA replication was inhibited. Here, we show that Cid12 is also required for faithful chromosome segregation and that mutation of amino acid residues predicted to be essential for poly(A) polymerase activity resulted in loss of Cid12 function in vivo. Cells lacking Cid12 had an increased chromosome segregation failure rate due to precocious loss of sister chromatid cohesion at the centromere but not along the chromosome arms. In keeping with a recently described function for Cid12 in RNA interference (RNAi)-mediated heterochromatin assembly, this was accompanied by an accumulation of polyadenylated transcripts corresponding to naturally silenced repeat elements within heterochromatic domains, with consequent defects in centromeric gene silencing. These cells also suffered increased meiotic defects, and their viability was dependent on the spindle checkpoint protein Bub1. To account for the effects of Cid12 on various aspects of DNA metabolism, including chromosome segregation and the checkpoint control, we suggest that Cid12 has dual functions in RNAi silencing and regulating mRNA stability.
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http://dx.doi.org/10.1128/MCB.02205-05 | DOI Listing |
Background: Mitosis maintains a genome's genetic information in daughter cells by accurately segregating chromosomes. However, chromosome aberrations are common during early mammalian embryogenesis. Chromosomal abnormalities during the early stages of embryogenesis result in the formation of mosaic embryos, wherein cells with normal genomes coexist with cells exhibiting abnormal genomes.
View Article and Find Full Text PDFReprod Med Biol
January 2025
Laboratory of Animal Reproduction, Graduate School of Agricultural Sciences Yamagata University Tsuruoka Japan.
Purpose: This study aimed to investigate the molecular mechanisms associated with chromosome segregation errors caused by intrinsic oxidative stress during in vitro oocyte maturation (IVM) using oocytes from -deficient (KO) mice.
Methods: Ovulated or in vitro matured cumulus-cells oocyte complexes (COCs) were collected from wild-type (WT) and KO mice and evaluated chromosome alignment, chromosome segregation, meiotic progression, and BUBR1 and REC8 protein expression levels.
Results: In 21% O IVM, the KO had significantly higher frequencies of chromosome misalignment and segregation errors compared to the WT, and they also reached Germinal Vesicle Break Down (GVBD) and M I stages peak earlier and showed a shorter M I stage residence time compared to the WT.
Sci Rep
January 2025
Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou City, No.199 Donggang West Road, 730000, Gansu Province, China.
Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of human epidermal growth factor receptor 2 (HER2) expression. Traditional Chinese medicine (TCM) has demonstrated promising efficacy in treating TNBC. This study explored the mechanisms of pachymic acid (PA) on TNBC by merging network pharmacology with experimental validation.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Obstetrics and Prenatal Medicine, Department of Gynecology and Obstetrics, University Hospital Frankfurt, J. W. Goethe-University, Frankfurt, Germany.
The protein regulator of cytokinesis 1 (PRC1) is a key regulator of microtubule crosslinking and bundling, which is crucial for spindle formation and cytokinesis. RITA, the BP-J nteracting and ubulin-ssociated protein, is a microtubule associated protein. We have reported that RITA localizes to mitotic spindles modulating microtubule dynamics and stability as well as to spindle poles affecting the activity of Aurora A.
View Article and Find Full Text PDFEMBO Rep
January 2025
Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Spindle assembly checkpoint (SAC) inhibitors are a recently developed class of drugs, which perturb chromosome segregation during cell division, induce chromosomal instability (CIN), and eventually lead to cell death. The molecular features that determine cellular sensitivity to these drugs are not fully understood. We recently reported that aneuploid cancer cells are preferentially sensitive to SAC inhibition.
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