A quantitative and semiautomated method for determining misaligned and Biology Diagrams As previously discussed, mitotic defects that escape detection and repair result in misaligned and anaphase lagging chromosomes prone to micronuclei formation and further genomic insults. Mitotic defects that produce CIN have been observed in tumors for over 100 years ().These defects include misaligned chromosomes that fail to align at the metaphase plate, chromosomes that lag behind the segregating masses of DNA late in mitosis, chromosomes that bridge the segregating DNA masses, and abnormal multipolar spindles that contain >2 spindle poles.
We observed an altered abundance of transcripts that encode mitotic regulators and mitotic chromosome misalignment defects following Btf and/or TRAP150 depletion. We propose that, in addition to their previously reported roles in maintaining mRNA distribution, Btf and TRAP150 control the abundance of transcripts encoding mitotic regulators Moreover, loss of POS3 results in prolonged mitosis, increased aneuploidy, and misaligned chromosomes near the spindle poles. Unexpectedly, we discovered a direct physical interaction and functional link between POS3 and the microtubule polymerase MICROTUBULE ORGANIZATION1 (MOR1) in regulating chromosome alignment and segregation during mitosis.
Micronuclei from misaligned chromosomes that satisfy the spindle ... Biology Diagrams
Defining mitotic cells in a Cartesian plane. (A) Representative images of mitotic cells with aligned and misaligned chromosomes. HeLa S3 cells were fixed and immunostained with CREST serum to mark the kinetochores, ฮณ-tubulin for the spindle poles, and ฮฑ-tubulin for the mitotic spindle. DNA was stained with Hoechst. Genome dynamics that support DSB repair rely on chromatin states, repair-protein condensates, nuclear or cytoplasmic microtubules and actin filaments, kinesin or myosin motor proteins, the nuclear Our data show that MCAK depletion or inhibition in mouse oocytes causes chromosome misalignment in mid-meiosis I, similar to in mitotic cells and Xenopus extracts, implying an imbalance of forces upon chromosomes. This suggests a role for MCAK in regulating MT interactions with the chromosome arms, and it is intriguing that MCAK is detectable
Chromosome alignment in human cells relies on the concerted action of motor-dependent and -independent mechanisms, which are determined by chromosome positioning at nuclear envelope breakdown (NEB), the establishment of end-on or lateral kinetochore-microtubule interactions and specific tubulin post-translational modifications. 1-8 Despite its key role in promoting mitotic fidelity, 9-11 Chromothripsis drives rapid genome evolution through the extensive shattering of mis-segregated chromosomes. This review discusses the cell cycle checkpoints that protect against mitotic errors, how mis-segregated chromosomes entrapped in abnormal nuclear structures undergo shattering, and the DNA damage response mechanisms that reassemble shattered chromosomes to generate complex cancer
