The origins and processing of ultra fine anaphase DNA bridges

Liu, Ying; Nielsen, Christian Friberg; Yao, Qi; Hickson, Ian D.

doi:10.1016/j.gde.2014.03.003

“…During DNA replication, sister chromatids become topologically intertwined and these catenane structures must be resolved by Topo IIα to permit chromosome segregation (Liu et al, 2014). Mutation of Smc5 in mESCs resulted in chromosome segregation defects reminiscent of a defect in Topo IIα function.…”

Section: Discussionmentioning

confidence: 99%

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

Pryzhkova¹,

Jordan²

2016

View full text Add to dashboard Cite

Correct duplication of stem cell genetic material and its appropriate segregation into daughter cells are requisites for tissue, organ and organism homeostasis. Disruption of stem cell genomic integrity can lead to developmental abnormalities and cancer. Roles of the Smc5/6 structural maintenance of chromosomes complex in pluripotent stem cell genome maintenance have not been investigated, despite its important roles in DNA synthesis, DNA repair and chromosome segregation as evaluated in other model systems. Using mouse embryonic stem cells (mESCs) with a conditional knockout allele of Smc5, we showed that Smc5 protein depletion resulted in destabilization of the Smc5/6 complex, accumulation of cells in G2 phase of the cell cycle and apoptosis. Detailed assessment of mitotic mESCs revealed abnormal condensin distribution and perturbed chromosome segregation, accompanied by irregular spindle morphology, lagging chromosomes and DNA bridges. Mutation of Smc5 resulted in retention of Aurora B kinase and enrichment of condensin on chromosome arms. Furthermore, we observed reduced levels of Polo-like kinase 1 at kinetochores during mitosis. Our study reveals crucial requirements of the Smc5/6 complex during cell cycle progression and for stem cell genome maintenance.

show abstract

“…The separation of sister centromeres requires the activity of Topo IIα (Liu et al, 2014). Previous studies on human Smc5/6-depleted RPE-1 cells have reported mislocalization of Topo IIα from pericentromeric regions to arms and distal ends of chromosomes (Gallego-Paez et al, 2014).…”

Section: Smc5-deficient Mescs Undergo Mitotic Catastrophementioning

confidence: 98%

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

Pryzhkova

¹

,

Jordan

²

2016

Journal of Cell Science

View full text Add to dashboard Cite

Correct duplication of stem cell genetic material and its appropriate segregation into daughter cells are requisites for tissue, organ and organism homeostasis. Disruption of stem cell genomic integrity can lead to developmental abnormalities and cancer. Roles of the Smc5/6 structural maintenance of chromosomes complex in pluripotent stem cell genome maintenance have not been investigated, despite its important roles in DNA synthesis, DNA repair and chromosome segregation as evaluated in other model systems. Using mouse embryonic stem cells (mESCs) with a conditional knockout allele of Smc5, we showed that Smc5 protein depletion resulted in destabilization of the Smc5/6 complex, accumulation of cells in G2 phase of the cell cycle and apoptosis. Detailed assessment of mitotic mESCs revealed abnormal condensin distribution and perturbed chromosome segregation, accompanied by irregular spindle morphology, lagging chromosomes and DNA bridges. Mutation of Smc5 resulted in retention of Aurora B kinase and enrichment of condensin on chromosome arms. Furthermore, we observed reduced levels of Polo-like kinase 1 at kinetochores during mitosis. Our study reveals crucial requirements of the Smc5/6 complex during cell cycle progression and for stem cell genome maintenance.

show abstract

“…3. Anaphase bridges and Ultrafine Anaphase Bridges [24] occur when a chromosome is stretched between two spindle poles during anaphase. The ultrafine bridges can be difficult to visualize using live-cell imaging, particularly when the stretched DNA is single-stranded.…”

Section: Does Aneuploidy Lead To Cin?mentioning

confidence: 99%

CIN and Aneuploidy: Different Concepts, Different Consequences

Schukken

¹

,

Foijer

²

2017

View full text Add to dashboard Cite

Chromosomal instability (CIN) and aneuploidy are similar concepts but not synonymous. CIN is the process that leads to chromosome copy number alterations, and aneuploidy is the result. While CIN and resulting aneuploidy often cause growth defects, they are also selected for in cancer cells. Although such contradicting fates may seem paradoxical at first, they can be better understood when CIN and aneuploidy are assessed separately, taking into account the in vitro or in vivo context, the rate of CIN, and severity of the aneuploid karyotype. As CIN can only be measured in living cells, which proves to be technically challenging in vivo, aneuploidy is more frequently quantified. However, CIN rates might be more predictive for tumor outcome than assessing aneuploidy rates alone. In reviewing the literature, we therefore conclude that there is an urgent need for new models in which we can monitor chromosome mis-segregation and its consequences in vivo. Also see the video abstract here: https://youtu.be/fL3LxZduchg

show abstract

The origins and processing of ultra fine anaphase DNA bridges

Cited by 119 publications

References 31 publications

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

CIN and Aneuploidy: Different Concepts, Different Consequences

Contact Info

Product

Resources

About