New mechanism discovered in meiosis

Inactivated, but still active – how modification of an enzyme governs critical processes in sexual reproduction.

'The Research Group' headed by molecular biologist Andrea Pichler from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany, has made an important discovery in meiosis research. Pichler and her group have identified a new mechanism in meiosis.

Meiosis, also called reductional division, is a key process in sexual reproduction. It shuffles parental genetic material which guarantees genetic variety.

In order to control various processes, cells can selectively alter properties of their proteins, such as protein lifespan, activity level, binding partners, or localization of proteins. This occurs by attaching one or more Small Ubiquitin-like Modifier (SUMO) proteins.

Alterations take place in three sequential enzyme-dependent steps. Scientists had assumed that the enzyme for step 2 was solely an intermediate step. However, the scientists in Freiburg have now discovered that the step-2 enzyme is itself modified by the SUMO protein which thereby alters how it functions.

The surprising effect: the conventional activity of the enzyme is switched off by this change and instead—becomes a new function.

The new function works together with the activated, unaltered enzyme in the formation of SUMO chains. If this effect is blocked, there are serious consequences: the protein structure (synaptonemal complex) that forms between the homologous chromosomes (chromosome pairs of approximately the same length, centromere position, and staining pattern) can no longer be established. Only a tiny amount – less than one percent – of the SUMO-modified step-2 enzyme is needed to form a normal protein structure (see image).

Researcher Helene Klug : “The smallest amount of the altered enzyme together with the unmodified enzyme is sufficient to form an active complex, which then carries out the meiosis specific SUMO modifications.”

Pichler, study leader, adds:“In the beginning, the results of the biological and biochemical experiments were completely contradictory, although the data were absolutely sound. We were therefore convinced that both sets of observations were correct. Explaining this contradiction led us then to the new mechanism.”

After fifty years of research on the synaptonemal complex, these new insights are setting a new course: “This is the first time we can study the loss of the synaptonemal complex with practically no secondary effects and we hope to unveil its secret. That allows us to investigate the consequences for meiosis and thus for development of the gametes,” say Franz Klein and Martin Xaver, collaborators and meiosis researchers at the Max F. Perutz Laboratories in Vienna.

Pichler and her team had demonstrated in 2008 that the step-2 enzyme in mammalian cells had an influence on precisely which proteins are tagged with SUMO. But, in order to uncover the biological mechanism of this form of regulation, the team switched to a simpler organism: baker’s yeast (Saccharomyces cerevisiae).

“Now that we know where to search, we want to switch back to the mammalian system and investigate the role of this enzyme regulation more closely,” says Pichler. “We want to better understand the function of the discovered baker’s yeast enzyme complex in the meiotic chromosomal structure.”

The work is published in Molecular Cell, 2 May 2013 Ubc9, "Sumoylation Controls SUMO Chain Formation and Meiotic Synapsis in Saccharomyces cerevisiae", by: Klug H, Xaver M, Chaugule V K, Koidl S, Mittler G, Klein F, and Pichler A
http://dx.doi.org/10.1016/j.molcel.2013.03.0

Scientists at the Max Planck Institute of Immunobiology and Epigenetics (MPI-IE) in Freiburg, founded in 1961, investigate how the immune system has developed over the course of evolution and how it changes during life. The focus on epigenetics was added in 2007. Researchers in this area investigate changes to inheritable characteristics that are not based upon changes to the DNA sequence.

Original article: http://www.mpg.de/7227575/meiosis