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What controls stickiness of 'smart' chromosomal glue

an ask, for example, what exactly happens to cohesins in older women that make them more likely to give birth to children with an abnormal chromosome number."

According to Amon, knowledge about the mechanism of cohesin function has remained sketchy, even though it plays a central role in meiosis. Researchers knew that an enzyme called separase snips apart cohesins, targeting a specific subunit of the cohesin complex called Rec8. Also, she said, researchers had found that Rec8 cleavage was promoted by phosphorylation -- the addition of chemical phosphate groups -- of Rec8.

Researchers also knew that cohesins release chromosome pairs from one another's embrace quite differently during meiosis and mitosis. In mitosis, cohesins release chromosomes along their entire length simultaneously. However, in the initial stage of meiosis, cohesins first release only the "arms" of chromosomes, still holding the chromosomes together at their central connection point, the centromere. Only in a second stage of meiosis that gives rise to haploid sperm or egg cells do centromeric cohesins become cleaved. This precisely controlled centromeric "stickiness" is essential for the accurate segregation of sister chromatids into separate cells.

"The key question we wanted to explore was how this step-wise loss of cohesins in meiosis was regulated," said Amon. "It could be that the enzyme separase was the key regulatory player, or it could be that it was the phosphorylation of cohesins that was central."

To find out, the researchers experimented with yeast cells, selectively mutating the Rec8 subunit so that it could not be phosphorylated. They then studied how the cell's inability to phosphorylate Rec8 affected meiosis. Those experiments showed that phosphorylation is, indeed, important for governing the step-wise loss of cohesins, said Amon. She also noted that research published in two complementary papers from the laboratories of Kim Nasmyth and Yoshinor
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Source:Howard Hughes Medical Institute


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