Related Experiment Video

Updated: Mar 18, 2026

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes
05:22

Generation and Isolation of Cell Cycle-arrested Cells with Complex Karyotypes

Published on: April 13, 2018

11.1K

Dynamic Bcl-xL (S49) and (S62) Phosphorylation/Dephosphorylation during Mitosis Prevents Chromosome Instability and

Prasamit Saurav Baruah1,2, Myriam Beauchemin1,2, Josée Hébert3,4

  • 1Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada.

Plos One
|July 12, 2016
PubMed

Insights

Dynamic phosphorylation of Bcl-xL protein at Ser49 and Ser62 is crucial for maintaining chromosome stability in normal human cells during mitosis, preventing senescence and aneuploidy.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Genetics

Background:

  • Bcl-xL protein phosphorylation at Ser49 and Ser62 is dynamic during mitosis.
  • Previous studies in tumor cells showed mitotic defects with Bcl-xL phosphorylation mutants.

Purpose of the Study:

  • To investigate the effects of Bcl-xL phosphorylation mutants on normal human diploid cells.
  • To determine if Bcl-xL phosphorylation is essential for chromosome integrity in non-cancerous cells.

Main Methods:

  • Generated Bcl-xL wild-type and phosphorylation mutant cell lines (S49A, S49D, S62A, S62D, S49/62A, S49/62D) in normal human diploid BJ foreskin fibroblast cells.
  • Assessed cell population doubling kinetics, senescence markers (β-galactosidase, IL-6, p53, p21Waf1/Cip1, γH2.X), cell death rates, and chromosome stability (FISH, karyotyping).

Main Results:

  • Bcl-xL phosphorylation mutants reduced cell population doubling kinetics and induced early senescence.
  • Senescent cells exhibited characteristic phenotypes, including elevated IL-6, p53, p21Waf1/Cip1, and γH2.X foci.
  • Expression of Bcl-xL mutants in normal cells led to chromosome instability and aneuploidy.

Conclusions:

  • Dynamic Bcl-xL phosphorylation at Ser49 and Ser62 is vital for maintaining chromosome integrity during mitosis in normal cells.
  • Disrupting Bcl-xL phosphorylation cycles can induce senescence and chromosome instability in normal cells.
  • Targeting Bcl-xL's mitotic function, not just its anti-apoptotic role, could offer novel cancer therapy strategies.

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

28.7K
Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH07:54

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Published on: August 19, 2014

17.6K

Related Concept Videos

Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.7K
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
51.4K
Meiosis II01:57

Meiosis II

Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each...
210.0K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.5K
Nondisjunction01:29

Nondisjunction

During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
83.2K
Nondisjunction01:21

Nondisjunction

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers.  Nondisjunction is common during anaphase I or anaphase II of meiosis.  Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
5.6K