Chromosome segregation regulator with possible link to Down’s syndrome identified

Written by Eleanor Ferguson

A recent thesis published in Nature Science claims to have discovered that further use of the enzyme PP2ACdc55 could theoretically help prevent disorders caused by chromosome mis-segration, such as Down’s syndrome and Edwards’s syndrome, as well as miscarriage.
The research identified a gene that regulates meiosis and suggests that presence of this enzyme allows for the regulation of the production of sperm and egg cells within the human reproduction process. Therefore, they believe it could aid prevention of chromosomal irregularity-related diseases and miscarriages, which are a result of errors in chromosome segregation within the human reproductive system.

The scientists – Gary W Kerr (University of Salford, Manchester, UK), Jin Huei Wong (A*STAR, Singapore) and Prakash Arumugam (National University of Singapore) – discovered new findings on the importance of the PP2ACdc55, previously investigated for a role in preventing the premature exit from meiosis: it plays a key role in the reduction of chromosome segregation (sometimes known as the ‘FEAR function’) during meiosis. Dr Kerr and colleagues stated that ‘’how meiosis is regulated’’ is of great importance for understanding ‘’causes of aneuploidy and genetic disorders in humans,” as little is known about the causes.

The investigation by the team consisted of three main stages. These stages showed that the presence of PP2ACdc55 in monopolar attachment prevents Cdc14 release from the nucleolus of yeast cells by counteracting phosphorylation of the nucleolar protein Net1 by Cdk (Cdc14 is an antagonizing phosphatase of Cdk).

The investigation was carried out through genetic screening and fluorescent tagging to track the ‘genetic switch’. By creating random mutations in the Cdc55 gene, the team analyzed the resulting mutant yeast strains. In the second stage, they individualized the mutations in order to emphasize the role of the gene by looking at the effect of the mutations on the resulting colonies.

Finally, they demonstrated the failure of the cell to form bipolar spindles, specifically there was no meiotic division. Concluding that spore viability is dramatically reduced, they suggested that PP2ACdc55 might play a vital role in meiotic chromosome segregation.

Although PP2ACdc55 plays an important role in chromosome segregation, and therefore continued presence of PP2ACdc55 within this process could potentially prevent certain conditions, it is still unknown how the process goes wrong and why. However, in terms of genetic and developmental research, this thesis could mark the next step towards aiding the prevention of conditions created within the human reproductive system.

Sources: Kerr G, Wong JH, Arumugam P. PP2ACdc55’s role in reductional chromosome segregation during achiasmate meiosis in budding yeast is independent of its FEAR function. Sci. Rep. DOI:10.1038/srep30397 (2016);