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The Journal of Cell Biology May 2023Enduring chromosome segregation errors represent potential threats to genomic stability due to eventual chromosome copy number alterations (aneuploidy) and formation of... (Review)
Review
Enduring chromosome segregation errors represent potential threats to genomic stability due to eventual chromosome copy number alterations (aneuploidy) and formation of micronuclei-key intermediates of a rapid mutational process known as chromothripsis that is found in cancer and congenital disorders. The spindle assembly checkpoint (SAC) has been viewed as the sole surveillance mechanism that prevents chromosome segregation errors during mitosis and meiosis. However, different types of chromosome segregation errors stemming from incorrect kinetochore-microtubule attachments satisfy the SAC and are more frequent than previously anticipated. Remarkably, recent works have unveiled that most of these errors are corrected during anaphase and only rarely result in aneuploidy or formation of micronuclei. Here, we discuss recent progress in our understanding of the origin and fate of chromosome segregation errors that satisfy the SAC and shed light on the surveillance, correction, and clearance mechanisms that prevent their transmission, to preserve genomic stability.
Topics: Humans; Anaphase; Aneuploidy; Chromosome Segregation; Kinetochores; Microtubules; Mitosis; Spindle Apparatus; Genomic Instability
PubMed: 37017932
DOI: 10.1083/jcb.202301106 -
Annual Review of Genetics Nov 2023The raison d'être of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are... (Review)
Review
The raison d'être of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are enabled by a complex cellular program in which interactions between homologous chromosomes play a central role. We first provide a background regarding the basic principles of this program. We then summarize the current understanding of the DNA events of recombination and of three processes that involve whole chromosomes: homolog pairing, crossover interference, and chiasma maturation. All of these processes are implemented by direct physical interaction of recombination complexes with underlying chromosome structures. Finally, we present convergent lines of evidence that the meiotic program may have evolved by coupling of this interaction to late-stage mitotic chromosome morphogenesis.
Topics: Chromosome Pairing; Meiosis; Chromosomes; DNA; Chromosome Segregation; Crossing Over, Genetic
PubMed: 37788458
DOI: 10.1146/annurev-genet-061323-044915 -
International Journal of Molecular... Mar 2022Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female... (Review)
Review
Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female reproduction contains two important aspects. One is the pool of oocytes in the human ovary (the ovarian reserve; approximately 10 at birth), which diminishes throughout life until menopause around the age of 50 (approximately 10 oocytes) in women. The second is the quality of oocytes, including the correctness of meiotic divisions, among other factors. Notably, the increased rate of sub- and infertility, aneuploidy, miscarriages, and birth defects are associated with advanced maternal age, especially in women above 35 years of age. This postponement is also relevant for human evolution; decades ago, the female aging-related fertility drop was not as important as it is today because women were having their children at a younger age. Spindle assembly is crucial for chromosome segregation during each cell division and oocyte maturation, making it an important event for euploidy. Consequently, aberrations in this segregation process, especially during the first meiotic division in human eggs, can lead to implantation failure or spontaneous abortion. Today, human reproductive medicine is also facing a high prevalence of aneuploidy, even in young females. However, the shift in the reproductive phase of humans and the strong increase in errors make the problem much more dramatic at later stages of the female reproductive phase. Aneuploidy in human eggs could be the result of the non-disjunction of entire chromosomes or sister chromatids during oocyte meiosis, but partial or segmental aneuploidies are also relevant. In this review, we intend to describe the relevance of the spindle apparatus during oocyte maturation for proper chromosome segregation in the context of maternal aging and the female reproductive lifespan.
Topics: Aging; Aneuploidy; Chromosome Segregation; Female; Humans; Meiosis; Oocytes; Pregnancy; Spindle Apparatus
PubMed: 35270022
DOI: 10.3390/ijms23052880 -
Cold Spring Harbor Perspectives in... Jul 2014A critical requirement for mitosis is the distribution of genetic material to the two daughter cells. The central player in this process is the macromolecular... (Review)
Review
A critical requirement for mitosis is the distribution of genetic material to the two daughter cells. The central player in this process is the macromolecular kinetochore structure, which binds to both chromosomal DNA and spindle microtubule polymers to direct chromosome alignment and segregation. This review will discuss the key kinetochore activities required for mitotic chromosome segregation, including the recognition of a specific site on each chromosome, kinetochore assembly and the formation of kinetochore-microtubule connections, the generation of force to drive chromosome segregation, and the regulation of kinetochore function to ensure that chromosome segregation occurs with high fidelity.
Topics: Cell Cycle Checkpoints; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Chromosome Segregation; Humans; Kinetochores; Microtubules; Mitosis; Spindle Apparatus
PubMed: 24984773
DOI: 10.1101/cshperspect.a015826 -
Molecular Cell Jun 2019The replisome quickly and accurately copies billions of DNA bases each cell division cycle. However, it can make errors, especially when the template DNA is damaged. In... (Review)
Review
The replisome quickly and accurately copies billions of DNA bases each cell division cycle. However, it can make errors, especially when the template DNA is damaged. In these cases, replication-coupled repair mechanisms remove the mistake or repair the template lesions to ensure high fidelity and complete copying of the genome. Failures in these genome maintenance activities generate mutations, rearrangements, and chromosome segregation problems that cause many human diseases. In this review, I provide a broad overview of replication-coupled repair pathways, explaining how they fix polymerase mistakes, respond to template damage that acts as obstacles to the replisome, deal with broken forks, and impact human health and disease.
Topics: Cell Cycle; Chromosome Segregation; DNA Damage; DNA Repair; DNA Replication; Genetic Diseases, Inborn; Genome, Human; Genomic Instability; Humans; Mutation
PubMed: 31173722
DOI: 10.1016/j.molcel.2019.04.027 -
Science (New York, N.Y.) Sep 2019Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed...
Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans.
Topics: Adolescent; Adult; Aging; Aneuploidy; Child; Chromosome Segregation; Female; Fertility; Humans; Meiosis; Nondisjunction, Genetic; Oocytes; Young Adult
PubMed: 31604276
DOI: 10.1126/science.aav7321 -
Journal of Bacteriology Nov 2019Reproduction in the bacterial kingdom predominantly occurs through binary fission-a process in which one parental cell is divided into two similarly sized daughter... (Review)
Review
Reproduction in the bacterial kingdom predominantly occurs through binary fission-a process in which one parental cell is divided into two similarly sized daughter cells. How cell division, in conjunction with cell elongation and chromosome segregation, is orchestrated by a multitude of proteins has been an active area of research spanning the past few decades. Together, the monumental endeavors of multiple laboratories have identified several cell division and cell shape regulators as well as their underlying regulatory mechanisms in rod-shaped and , which serve as model organisms for Gram-negative and Gram-positive bacteria, respectively. Yet our understanding of bacterial cell division and morphology regulation is far from complete, especially in noncanonical and non-rod-shaped organisms. In this review, we focus on two proteins that are highly conserved in Gram-positive organisms, DivIVA and its homolog GpsB, and attempt to summarize the recent advances in this area of research and discuss their various roles in cell division, cell growth, and chromosome segregation in addition to their interactome and posttranslational regulation.
Topics: Bacillus subtilis; Bacterial Proteins; Cell Division; Cell Proliferation; Chromosome Segregation; Protein Processing, Post-Translational
PubMed: 31405912
DOI: 10.1128/JB.00245-19 -
Current Biology : CB Jun 2015The terms 'haploid' and 'diploid' that describe single (n) and double (2n) chromosome sets in cells were coined by the Polish-German botanist Eduard Strasburger and...
The terms 'haploid' and 'diploid' that describe single (n) and double (2n) chromosome sets in cells were coined by the Polish-German botanist Eduard Strasburger and originate from the Greek terms haplóos meaning 'single' and diplóos meaning 'double'. The term 'ploidy' was subsequently derived to describe the total chromosome content of cells. Consequently, the term 'euploid' refers to a chromosome complement that is an exact multiple of the haploid number. Therefore, haploids and diploids are both cases of normal euploidy. Euploid types that have more than two sets of chromosomes are 'polyploid' such as 'triploid' (3n), 'tetraploid' (4n), 'pentaploid' (5n), and so forth. There are various natural euploid states with some organisms existing as haploids (fungi), diploids (most mammals), and polyploids (plants).
Topics: Aneuploidy; Cell Proliferation; Chromosome Segregation; Gene Dosage; Humans; Kinetochores; Models, Genetic; Phenotype; Spindle Apparatus; Telomere
PubMed: 26126276
DOI: 10.1016/j.cub.2015.05.010 -
Developmental Cell May 2017In this issue of Developmental Cell, Kyogoku and Kitajima (2017) investigate the effect of cytoplasmic volume on the fidelity of chromosome segregation during meiosis in... (Review)
Review
In this issue of Developmental Cell, Kyogoku and Kitajima (2017) investigate the effect of cytoplasmic volume on the fidelity of chromosome segregation during meiosis in mouse oocytes. The authors find that large cytoplasmic volume affects spindle pole morphology, chromosome alignment, and stringency of checkpoint signaling, resulting in error-prone chromosome segregation.
Topics: Animals; Cell Cycle Checkpoints; Chromosome Segregation; Cytoplasm; Humans; Meiosis; Oocytes; Spindle Apparatus
PubMed: 28486126
DOI: 10.1016/j.devcel.2017.04.015 -
Cells Feb 2021Chromosome segregation-the partitioning of genetic material into two daughter cells-is one of the most crucial processes in cell division. In all Eukaryotes, chromosome... (Review)
Review
Chromosome segregation-the partitioning of genetic material into two daughter cells-is one of the most crucial processes in cell division. In all Eukaryotes, chromosome segregation is driven by the spindle, a microtubule-based, self-organizing subcellular structure. Extensive research performed over the past 150 years has identified numerous commonalities and contrasts between spindles in different systems. In this review, we use simple coarse-grained models to organize and integrate previous studies of chromosome segregation. We discuss sites of force generation in spindles and fundamental mechanical principles that any understanding of chromosome segregation must be based upon. We argue that conserved sites of force generation may interact differently in different spindles, leading to distinct mechanical mechanisms of chromosome segregation. We suggest experiments to determine which mechanical mechanism is operative in a particular spindle under study. Finally, we propose that combining biophysical experiments, coarse-grained theories, and evolutionary genetics will be a productive approach to enhance our understanding of chromosome segregation in the future.
Topics: Chromosome Segregation; Humans
PubMed: 33671543
DOI: 10.3390/cells10020465