User:Gao.Ya/sandbox
Mitotic catastrophe, a type of programmed cell death, or PCD that takes place when a cell is destroyed as a result of an aberrant
There are two distinguishable subtypes of mitotic catastrophe. First, mitotic catastrophe can kill the cell during or close to the metaphase, in a
.
Discovery
In 1989, Lisa Moiz and her collaborators observed mitotic catastrophe in
Definition
During recent years, the term of “mitotic catastrophe” has been widely used to describe a kind of cell death that affects mammalian cells. But no accurate and accepted definition of mitotic catastrophe has been made. Igor Rominson, a senior scientist of Ordway Research Institute, defined mitotic catastrophe in morphological terms as a type of cell death resulting from abnormal mitosis, which usually ends in the formation of large cells with multiple micronuclei and decondensed chromatin [1]. It shows some phenotypic characteristic of apoptosis such as hypercondensed chromatin aggregates.
Morphological characteristics
There is no complete description of morphological characteristics of mitotic catastrophe. However, the major morphological trait is the formation of a macro cell that contains several nuclei and condensed chromatin. There has been a debate that the chromosome condensation in apoptosis is the same as that in mitotic catastrophe. It is clear that if a cell fails to block its process of
Regulation factors
Cdk1/cyclin B1 complex
The
DNA damage sensors and Chk2
Mitotic catastrophe can be avoided by an intact DNA structure checkpoint. Usually, DNA damage such as
and so on, then relayed to kinases. But kinase Chk2 can stop the cell cycle. Chk2 is a negative regulator of mitotic catastrophe in human cells. The inhibition of Chk2 prevents the activation of a DNA structure check point, which will arrest the cell cycle. Polyploid cells will arrest at the early prophase of the cell cycle, correlating with a sudden loss of cyclin B1 and then undergo mitotic catastrophe [1].Application in cancer treatment
After failure to activate the G2/M checkpoints, cells with DNA damage activate an apoptotic program that leads to the formation of mitotic catastrophe during metaphase of the cell cycle. Suppression of the apoptotic program may cause the abnormal cell division, resulting into the creation of tetraploid cells. These cells can generate aneuploid offspring. Since mitotic catastrophe happens when a cell is destroyed during mitosis by aberrant chromosome segregation and DNA damage, and cells in mitotic catastrophe are likely to create aneuploid cells, posing a risk of oncogenesis. Because the mechanisms of mitotic catastrophe often triggered in cancer cells and tissues in response to anti-cancer drugs, chemotherapeuticals induce cell death via these routes during the course of mitosis[3] Hence, mitotic catastrophe is also in the league of processes which participate in prevention of cancer. It can be stimulated by ionizing radiations (IR), chemotherapeutic drugs or hyperthermia and is caused by malfunctioning of cell cycle checkpoints [3]. How the mitotic catastrophe is induced could be important for cancer treatment.
References:
- ^ a b c d e f Maria Castedo, Jean-Luc Perfettin, Thomas Roumier, Karine Andreau, Rene Medema and Guido Kroemer, Cell death by mitotic catastrophe: a molecular definition. Oncogene,2004, 23, 2825-2837.
- ^ a b Margottin-Goguet F,Hsu JY,Loktev A,et al.Prophase destruction of Emi1 by the SCF (betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.[J].Dev Cell.2003,4:813-826.
- ^ a b Richa Singh, Jasmine George, Yogeshwer Shukla. Role of senescence and mitotic catastrophe in cancer therapy. Cell Division 2010,5;4.