Will have major impact on understanding of genome stability and birth defects

A multi-university team of researchers have for the first time determined how the proteasome, the machinery that in all living cells destroys proteins after they have completed their function, controls key processes of chromosome segregation during meiosis. These findings shed new light on how protein degradation controls cellular functions and could have major implications for our understanding of how errors in chromosome stability can lead to birth defects and cancer. The findings were published online by the journal Science on Thursday, January 5.

Meiosis is a specialized cell division used for gamete formation by all sexually reproducing organisms, including animals, plants, and humans. During meiosis the proteasome assists in regulating the concentration of particular proteins and degrading misfolded proteins, in a process known as proteolysis. However, the significant impact of proteolytic activity on events leading up to chromosome segregation during meiosis was unknown until now.

“Key events of meiosis involve the pairing and crossing over between homologous chromosomes,” says Valentin B??rner, leader of the research team and an associate professor with Cleveland State University’s Center for Gene Regulation in Health and Disease. “Our findings show that the proteasome controls both processes via its proteolytic activity. Errors in this activity could be the reason for chromosomal instabilities which cause miscarriages, birth defects such as Down syndrome and cancer. This is the first case where proteolytic activity has been implicated in large-scale changes in chromosome pairing.”

B??rner’s team also found that proteasomes are specifically recruited to chromosomes as part of a cellular differentiation program. Previously, it had been widely assumed that proteasome-substrate interactions were opportunistic.

“This represents a paradigm shift in our understanding of how the proteasome actually interacts with chromosomes,” adds B??rner who also serves as a research scientist with the Case Comprehensive Cancer Center at Case Western Reserve University. “It will greatly inform our efforts to better map how protein degradation affects chromosome stability in cells and how defects in these processes impact human health.”

B??rner’s team also included researchers from the University of Pittsburgh School of Medicine and Washington State University.

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