Different outcomes of telomere-dependent anaphase bridges

2010 ◽  
Vol 38 (6) ◽  
pp. 1698-1703 ◽  
Author(s):  
Laura Tusell ◽  
Judit Pampalona ◽  
David Soler ◽  
Cristina Frías ◽  
Anna Genescà
Keyword(s):  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Chromosome Rearrangements ◽  
Genetic Changes ◽  
Anaphase Bridges ◽  
Chromosome Aneuploidy ◽  
Chromatin Bridge ◽  
Cell Immortalization ◽  
Chromosome Fusions ◽  
Telomere Erosion

Chromosomal instability occurs early in the development of cancer and may represent an important step in promoting the multiple genetic changes required for the initiation and/or progression of the disease. Telomere erosion is one of the factors that contribute to chromosome instability through end-to-end chromosome fusions entering BFB (breakage–fusion–bridge) cycles. Uncapped chromosomes with short dysfunctional telomeres represent an initiating substrate for both pre- and post-replicative joining, which leads to unstable chromosome rearrangements prone to bridge at mitotic anaphase. Resolution of chromatin bridge intermediates is likely to contribute greatly to the generation of segmental chromosome amplification events, unbalanced chromosome rearrangements and whole chromosome aneuploidy. Accordingly, telomere-driven instability generates highly unstable genomes that could promote cell immortalization and the acquisition of a tumour phenotype.

scholarly journals DNA-Replikationsstress, Mitose und genomische Instabilität

BIOspektrum ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 10-13
Author(s):  
Alicia Konrath ◽  
Ann-Kathrin Schmidt ◽  
Holger Bastians
Keyword(s):  
Dna Replication ◽  
Tumor Progression ◽  
Chromosome Aberrations ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Functional Link ◽  
Structural Chromosome ◽  
Genomische Instabilität

AbstractChromosomal instability (CIN) is a hallmark of cancer and contributes to tumorigenesis and tumor progression. While structural CIN (S-CIN) leads to structural chromosome aberrations, whole chromosome instability (W-CIN) is defined by perpetual gains or losses of chromosomes during mitosis causing aneuploidy. Mitotic defects, but also abnormal DNA replication (replication stress) can lead to W-CIN. However, the functional link between replication stress, mitosis and aneuploidy is little understood.

scholarly journals The wages of CIN

2008 ◽  
Vol 180 (4) ◽  
pp. 661-663 ◽  
Author(s):  
Karen W. Yuen ◽  
Arshad Desai
Keyword(s):  
Cancer Cells ◽  
Solid Tumors ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Spindle Checkpoint ◽  
Human Cells ◽  
Normal Cells ◽  
Chromosome Missegregation ◽  
Cell Biol ◽  
The Relationship

Aneuploidy and chromosome instability (CIN) are hallmarks of the majority of solid tumors, but the relationship between them is not well understood. In this issue, Thompson and Compton (Thompson, S.L., and D.A. Compton. 2008. Examining the link between chromosomal instability and aneuploidy in human cells. J. Cell. Biol. 180:665–672) investigate the mechanism of CIN in cancer cells and find that CIN arises primarily from defective kinetochore–spindle attachments that evade detection by the spindle checkpoint and persist into anaphase. They also explore the consequences of artificially elevating chromosome missegregation in otherwise karyotypically normal cells. Their finding that induced aneuploidy is rapidly selected against suggests that the persistence of aneuploid cells in tumors requires not only chromosome missegregation but also additional, as yet poorly defined events.

CHROMOSOMAL INSTABILITY IN A HYBRID BETWEEN HORDEUM VULGARE AND SECALE VAVILOVII

1982 ◽  
Vol 24 (2) ◽  
pp. 207-212 ◽  
Author(s):  
George Fedak ◽  
Chiharu Nakamura
Keyword(s):  
Hordeum Vulgare ◽  
Chromosome Number ◽  
Chiasma Frequency ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Somatic Tissue ◽  
Unreduced Gamete ◽  
Hordeum Vulgare L ◽  
The Mean

A hybrid was obtained between Hordeum vulgare L. cv. Betzes (2n = 2x = 14) and Secale vavilovii [Nürn. (2n = 2x = 14)] in which chromosome instability was observed in somatic and meiotic tissues. In somatic tissue the chromosomes per cell varied from 7 to 24 with a mean of 19.7. Similarly in meiotic tissue the chromosome number varied from 14 to 26 with a mean of 18.3. The mean chiasma frequency was 12.9 consisting of an average Ml configuration of 0.02IV + 0.3III + 6.68II + 3.92I. It was concluded that the hybrid was derived from the union of an unreduced gamete from Betzes barley with a normal gamete from S. vavilovii.

scholarly journals Loss of BubR1 Acetylation instigates Replication Stress leading to Complex Chromosomal Rearrangement in tumors

2019 ◽  
Author(s):  
Jiho Park ◽  
Song-Yion Yeu ◽  
Sangjin Paik ◽  
Junyeob Lee ◽  
Jinho Jang ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Chromosome Structure ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Chromosome Rearrangements ◽  
Mouse Tumors ◽  
Genome Wide ◽  
Deficient Mice ◽  
Complex Chromosome ◽  
Double Mutant Mouse

AbstractChromosome number and structure instability is the hallmark of cancer. Equal chromosome segregation is guaranteed by the spindle assembly checkpoint (SAC), thus defective SAC leads to chromosome instability. However, aneuploidy alone is not oncogenic, and whether compromised SAC is associated with structure instability remains elusive. BubR1 is a core component of SAC, which is acetylated at lysine 250 in mitosis. Previously, we showed that deficiency of BubR1 acetylation in mice (K243R/+) leads to spontaneous tumorigenesis via chromosome mis-segregation. Here, we asked whether loss of BubR1 acetylation is associated with chromosome structure instability by examiningK243R/+mice intercrossed top53-deficient mice. Genome-wide sequencing and spectral karyotyping of the double mutant mouse tumors revealed that BubR1 acetylation deficiency leads to complex chromosome rearrangements, including Robertsonian-like whole-arm translocations and premature sister-chromatid separations (PMSCS). In primary MEFs, replication stress was markedly increased in telomeres and centromeres, suggesting that the replication stress underlies the significant increase of DNA damage and subsequent chromosome rearrangements. Furthermore, defects in BubR1 acetylation at K250 were detected in human cancers as well. Collectively, we propose that chromosome mis-segregation by the loss of BubR1 acetylation causes chromosome structure instability, leading to massive chromosome rearrangements through the induction of replication stress.

scholarly journals DNA Stability Contrasts with Chromosome Variability in Allium Fistulosum Calli

2014 ◽  
Vol 56 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Patryk Mizia ◽  
Dagmara Kwolek ◽  
Tomasz Ilnicki
Keyword(s):  
Genetic Similarity ◽  
Chromosomal Instability ◽  
Selection Pressure ◽  
Dna Polymorphism ◽  
Rapd Analysis ◽  
Polymorphic Band ◽  
Genetic Changes ◽  
Band Frequency ◽  
Callus Lines

Abstract RAPD analysis was applied to assess the degree of DNA polymorphism in A. fistulosum calli of high chromosomal instability. Nineteen of 24 randomly selected RAPD primers revealed scorable polymorphism between calli and seeds (reference material). Polymorphic band frequency was 55/237 in seeds and 36/233 in calli; variability on the DNA level was thus lower in calli than in seeds (15.4% vs. 23.2% of band positions). UPGMA analysis of Jaccard's coefficients confirmed the genetic similarity of the analyzed cultures. The most distinctive DNA changes in calli involved coincident loss of original bands or the appearance of novel bands. Seven such changes (4 losses, 3 gains) were observed. Our results suggest that changes on the chromosomal level and on the DNA level occurred independently of each other and that different callus lines underwent similar genetic changes during culture, presumably due to strong selection pressure effected by standard in vitro conditions.

scholarly journals Dormant replication origin firing links replication stress to whole chromosomal instability in human cancer

2021 ◽  
Author(s):  
Ann-Kathrin Schmidt ◽  
Nicolas Boehly ◽  
Xiaoxiao Zhang ◽  
Benjamin O. Slusarenko ◽  
Magdalena Hennecke ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Chromosomal Instability ◽  
Replication Origin ◽  
Human Cancer ◽  
Chromosome Instability ◽  
Replication Stress ◽  
S Phase ◽  
Origin Firing ◽  
Human Cancer Cells ◽  
Chromosome Missegregation

Chromosomal instability (CIN) is a hallmark of cancer and comprises structural CIN (S-CIN) and whole chromosome instability (W-CIN). Replication stress (RS), a condition of slowed or stalled DNA replication during S phase, has been linked to S-CIN, whereas defects in mitosis leading to chromosome missegregation and aneuploidy can account for W-CIN. It is well established that RS can activate additional replication origin firing that is considered as a rescue mechanism to suppress chromosomal instability in the presence of RS. In contrast, we show here that an increase in replication origin firing during S phase can contribute to W-CIN in human cancer cells. Increased origin firing can be specifically triggered by overexpression of origin firing genes including GINS1 and CDC45, whose elevated expression significantly correlates with W-CIN in human cancer specimens. Moreover, endogenous mild RS present in cancer cells characterized by W-CIN or modulation of the origin firing regulating ATR-CDK1-RIF1 axis induces dormant origin firing, which is sufficient to trigger chromosome missegregation and W-CIN. Importantly, chromosome missegregation upon increased dormant origin firing is mediated by increased microtubule growth rates leading to the generation of lagging chromosomes in mitosis, a condition prevalent in chromosomally unstable cancer cells. Thus, our study identified increased or dormant replication origin firing as a hitherto unrecognized, but cancer-relevant trigger for chromosomal instability.

Dynamics of telomeric chromatin at the crossroads of aging and cancer

2010 ◽  
Vol 48 ◽  
pp. 147-164 ◽  
Author(s):  
Jing Ye ◽  
Yunlin Wu ◽  
Eric Gilson
Keyword(s):  
Chromosomal Instability ◽  
Cellular Proliferation ◽  
Human Cancer ◽  
Chromosome Instability ◽  
Telomere Dysfunction ◽  
Promising Candidate ◽  
Telomere Shortening ◽  
Anti Cancer ◽  
Protein Components

Telomeres are nucleoprotein structures that protect the ends of human chromosomes through the formation of a ‘cap’, thus preventing exonucleolytic degradation, inter- and intra-chromosomal fusion, and subsequent chromosomal instability. During aging, telomere shortening correlates with tissue dysfunction and loss of renewal capacity. In human cancer, telomere dysfunction is involved in early chromosome instability, long-term cellular proliferation, and possibly other processes related to cell survival and microenvironment. Telomeres constitute an attractive target for the development of novel small-molecule anti-cancer drugs. In particular, individual protein components of the core telomere higher-order chromatin structure (known as the telosome or ‘shelterin’ complex) are promising candidate targets for cancer therapy.

scholarly journals The p53/p73 - p21CIP1 tumor suppressor axis guards against chromosomal instability by restraining CDK1 in human cancer cells

Oncogene ◽  
2020 ◽  
Author(s):  
Ann-Kathrin Schmidt ◽  
Karoline Pudelko ◽  
Jan-Eric Boekenkamp ◽  
Katharina Berger ◽  
Maik Kschischo ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Genes ◽  
Chromosomal Instability ◽  
Target Gene ◽  
Human Cancer ◽  
Chromosome Instability ◽  
Microtubule Assembly ◽  
Cdk Inhibitor ◽  
Human Cancer Cells

Abstract Whole chromosome instability (W-CIN) is a hallmark of human cancer and contributes to the evolvement of aneuploidy. W-CIN can be induced by abnormally increased microtubule plus end assembly rates during mitosis leading to the generation of lagging chromosomes during anaphase as a major form of mitotic errors in human cancer cells. Here, we show that loss of the tumor suppressor genes TP53 and TP73 can trigger increased mitotic microtubule assembly rates, lagging chromosomes, and W-CIN. CDKN1A, encoding for the CDK inhibitor p21CIP1, represents a critical target gene of p53/p73. Loss of p21CIP1 unleashes CDK1 activity which causes W-CIN in otherwise chromosomally stable cancer cells. Consequently, induction of CDK1 is sufficient to induce abnormal microtubule assembly rates and W-CIN. Vice versa, partial inhibition of CDK1 activity in chromosomally unstable cancer cells corrects abnormal microtubule behavior and suppresses W-CIN. Thus, our study shows that the p53/p73 - p21CIP1 tumor suppressor axis, whose loss is associated with W-CIN in human cancer, safeguards against chromosome missegregation and aneuploidy by preventing abnormally increased CDK1 activity.

Sign in / Sign up

Export Citation Format

Share Document