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Dev Cell
Wellcome Trust Centre for Gene Regulation & Expression, University of Dundee, Dundee DD1 5EH, UK.
Published: February 2010
In early mitosis, microtubules can be generated at kinetochores as well as at spindle poles. However, the role and regulation of kinetochore-derived microtubules have been unclear. In general, metaphase spindle microtubules are oriented such that their plus ends bind to kinetochores. However, we now have evidence that, during early mitosis in budding yeast, microtubules are generated at kinetochores with distal plus ends. These kinetochore-derived microtubules interact along their length with microtubules that extend from a spindle pole, facilitating kinetochore loading onto the lateral surface of spindle pole microtubules. Once kinetochores are loaded, microtubules are no longer generated at kinetochores, and those that remain disappear rapidly and do not contribute to the metaphase spindle. Stu2 (the ortholog of vertebrate XMAP215/ch-TOG) localizes to kinetochores and plays a central role in regulating kinetochore-derived microtubules. Our work provides insight into microtubule generation at kinetochores and the mechanisms that facilitate initial kinetochore interaction with spindle pole microtubules.
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http://dx.doi.org/10.1016/j.devcel.2009.12.018 | DOI Listing |
Curr Opin Cell Biol
February 2025
Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom. Electronic address:
Meiosis generates gametes through a specialised cell cycle that reduces the genome by half. Homologous chromosomes are segregated in meiosis I and sister chromatids are segregated in meiosis II. Centromeres and kinetochores play central roles in instructing this specialised chromosome segregation pattern.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2024
General Surgery/Gastrointestinal Surgery, Fuyang District First People's Hospital of Hangzhou, Fuyang District, Hangzhou, China.
Colorectal cancer refers to malignant tumors occurring in the walls of the colon or rectum. The roles of WD Repeat Domain 12 (WDR12) and mitochondrial ribosome-associated tumor suppressor 4 (MRTO4) genes in colorectal cancer remain unclear. The colorectal cancer dataset GSE113513 configuration file was downloaded from the gene expression omnibus database generated from GPL15207.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University Health Science Center, 410013 Changsha, Hunan, China.
Background: α thalassemia/mental retardation syndrome X-linked (ATRX) serves as a part of the sucrose nonfermenting 2 (SNF2) chromatin-remodeling complex. In interphase, ATRX localizes to pericentromeric heterochromatin, contributing to DNA double-strand break repair, DNA replication, and telomere maintenance. During mitosis, most ATRX proteins are removed from chromosomal arms, leaving a pool near the centromere region in mammalian cells, which is critical for accurate chromosome congression and sister chromatid cohesion protection.
View Article and Find Full Text PDFNat Med
February 2025
University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.
View Article and Find Full Text PDFNucleic Acids Res
February 2025
Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) OT Gatersleben, Corrensstr 3, 06466 Seeland, Germany.
In eukaryotes, accurate chromosome segregation during cell division relies on the centromeric histone H3 variant, CENH3. Our previous work identified KINETOCHORE NULL2 (αKNL2) as a plant CENH3 assembly factor, which contains a centromere-targeting motif, CENPC-k, analogous to the CENPC motif found in CENP-C. We also demonstrated that αKNL2 can bind DNA in vitro in a sequence-independent manner, without the involvement of its CENPC-k motif.
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