Master Regulator Of Chromosomal Segregation Identified

The identity of the evolutionarily conserved meiosis regulator Meikin could advance treatments for fertility or Down’s syndrome.

AsianScientist (Mar. 10, 2015) – Scientists have identified the master regulator of chromosome segregation during meiosis, an important process involved during the production of egg and sperm cells. Their results, published in Nature, could have implication on fertility and conditions such as Down’s syndrome.

There are two types of cell division: mitosis, which is observed in somatic cells such as skin, and meiosis, which occurs in the germ cells that produce sperm and eggs and reduces the chromosomes in half. In mitosis, the replicated chromosomes (sister chromatids) are segregated equationally, with one sister chromatid moving to each spindle pole.

In meiosis, however, homologous chromosomes (one chromosome from each parent) rather than sister chromatids are separated. This is because the homologous chromosomes, combined by chiasmata at which genetic information is exchanged, are captured from opposite poles of the cell in an additional reductional division that halves the number of chromosomes.

Schematic diagram of chromosome segregation in mitosis (left) and meiosis (right). In meiosis, Meikin, the master regulator discovered in this study, is expressed and localized to kinetochores, endowing them with the function of mono-orientation and cohesion protection. Credit: Yoshinori Watanabe/University of Tokyo.
Schematic diagram of chromosome segregation in mitosis (left) and meiosis (right). In meiosis, Meikin, the master regulator discovered in this study, is expressed and localized to kinetochores, endowing them with the function of mono-orientation and cohesion protection. Credit: Yoshinori Watanabe/University of Tokyo.

It is known that during this reductional division the duplicated chromosomes are captured only from one spindle and remain attached throughout anaphase. Although the existence of a master regulator of meiotic chromosome segregation has been anticipated, its identity has remained elusive.

In the present study, the research group of Project Researcher Kim Jihye and Professor Yoshinori Watanabe at the University of Tokyo Institute of Molecular and Cellular Biosciences identified a novel kinetochore protein in mouse germ cells which they have named Meikin (meiosis-specific kinetochore protein).

In knockout mice unable to express the Meikin gene, kinetochore mono-orientation and the protection of cohesion, two characteristics of reductional division, are both defective. Thus, the researchers conclude that Meikin is the long-awaited master regulator of meiotic chromosome segregation. In addition, the researchers showed from an analysis of mice and yeast that the mechanism of chromosome separation in germ cells is conserved in many living organisms including humans.

Older human eggs contain an abnormal number of chromosomes found in high frequency, and this is known to be a major cause of birth defects such as Down syndrome. The current findings are expected to contribute significantly to elucidating the cause of infertility or Down’s syndrome in humans.

The article can be found at: Kim et al. (2015) Meikin is a Conserved Regulator of Meiosis-I-Specific Kinetochore Function.

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Source: University of Tokyo.
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