Cutting the ties that bind

During the formation of eggs and sperm, the cell’s chromosomes must pair up and part in an elaborate sequence that results in sex cells with exactly half the number of chromosomes as the parent cell. In this process, called meiosis, a single misstep can cause infertility, miscarriage, or birth defects.

To stay properly paired, most chromosomes use a process called crossing over, where they loop chromosome arms with their partners and even swap genetic material. Other chromosomes are too short to make these crossovers, but they are still able to stay connected to their partners.

Recent research using a fruit fly model system has shown that some shorter chromosomes stay connected by using thin threads of DNA to tether themselves together, but how they come untied again has not been clear. Stowers Institute scientists now report that an enzyme called Topoisomerase II is required for these entangled chromosomes to be set free.

“It is not surprising there are many ways to segregate chromosomes because there are also many ways to control other molecular events, like gene expression,” says R. Scott Hawley, PhD, a Stowers Institute investigator and American Cancer Society Research Professor who led the study.

Hawley Lab Research Associate II Stacie E. Hughes, PhD, explains, “Without this enzyme the chromosomes can’t come apart, they are stuck together like glue. There are large regions of the chromosomes that are tethered together by these threads, while the rest is stretched out like a slinky as the chromosomes are pulled in opposite directions. It is just a mess. Because the chromosomes are just stuck there, they can’t finish meiosis.”

By showing that Topoisomerase II is required for resolving these threads so homologous chromosomes can part ways, the Hawley lab team underscores the complexity of the meiotic process.

This study was published in the October 23, 2014, issue of PLoS Genetics.