Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bayreuth geneticists discover regulatory mechanism of chromosome inheritance

09.04.2020

In the course of every single cell division, the genetic information on the chromosomes must be distributed equally between the newly developing daughter cells. The enzyme separase plays a decisive role in this process. Susanne Hellmuth and Olaf Stemmann from the Chair of genetics at the University of Bayreuth have now discovered a previously unknown mechanism that regulates the activity of the separase. These fundamental findings add a new aspect to our current understanding of chromosome inheritance. The scientists have presented their study in the journal "Nature".

Crucial for healthy cell development: the regulation of separase


Susanne Hellmuth M. Sc, PhD student at the Department of Genetics at the University of Bayreuth, here loading samples for the separation of proteins and their subsequent immunological detection.

Images: Olaf Stemmann


The separase cuts the cohesin rings, which hold the sister chromatids together. These then migrate to the opposite poles of the spindle apparatus.

Graphic: Olaf Stemmann

Cell division is essential for human growth and reproduction. Before a cell begins to divide, the genetic information stored on the chromosomes is duplicated. When this process is complete, each chromosome consists of two identical DNA threads, the sister chromatids.

Cohesin, a ring consisting of several proteins, encloses each chromosome and holds the pair of chromatids together. Already during preparation for cell division, cohesin is removed from the arms of the chromosomes. However, the complete separation of the sister chromatids can only take place when the cohesin remaining in the middle of the chromosomes is cut by the enzyme separase. The chromatids then migrate to the two opposite ends of the spindle apparatus, where they form the genetic basis of the forming daughter cells.

Healthy development of the daughter cells is only guaranteed if they do not contain genetic defects. In order for this condition to be fulfilled, the separase must become active at exactly the right time. If the sister chromatids are separated too early, they can only be distributed randomly. The resulting daughter cells then contain the wrong chromosome number and die, or they can develop into tumour cells. Only strict regulation of the separase prevents these genetic malfunctions.

A "guardian spirit" suppresses premature sister chromatid separation

The Bayreuth researchers Susanne Hellmuth and Olaf Stemmann, in cooperation with geneticists from the University of Salamanca/Spain, have now discovered that the protein shugoshin (Japanese for "guardian spirit") has exactly this regulating function. Shugoshin causes the separase to remain inactive until the right time for cohesin splitting has come.

With this discovery, scientists have succeeded in solving an important puzzle of genetics: Until now, only the protein securin was known to suppress premature activity of the separase. It was therefore believed that the separase was exclusively regulated by securin. However, this view contradicted the observation that separase remains properly regulated even when securin is not present.

The study now published in "Nature" provides the explanation: Shugoshin and securin both prevent separase from initiating the process of chromsosome segregation at the wrong time. And if the securin fails, even shugoshin alone is able to regulate the activity of separase in human cells.

"We are dealing with a type of redundancy that is not at all uncommon in the cell cycle: In order for a vital process to proceed in a well-ordered manner, nature has safeguarded it by controlling it simultaneously in two or more different ways. This makes the process particularly robust, but also difficult to study, because individual disturbances have no visible effect," said Susanne Hellmuth, first author of the study.

Dual control through the spindle checkpoint

Indeed, Hellmuth and Stemmann made a further discovery: It is the spindle assembly checkpoint (SAC) that controls the regulating influence of shugoshin as well as that of securin. This finding confirms the well-established assumption in the research that the SAC has, as it were, sovereignty over all processes involved in chromosome inheritance.

It had been known for some time that the SAC first stabilizes the securin and does not allow its degradation until the time has come for cohesin splitting by separase. The "Nature" publication now shows how the checkpoint causes shugoshin to suppress the premature activity of separase: namely by associating shugoshin with the SAC component Mad2.

"I was particularly pleased to hear a remark on our publication by one referee that the textbooks will now have to be rewritten," says Olaf Stemmann. "Our further research will show how our fundamental findings could also find their way into cancer therapy." This follow-up study by the Bayreuth research duo will also soon be published in "Nature".

Research funding:

The research work at the University of Bayreuth was funded by the German Research Foundation (DFG). Their research partners in Spain received funding from the Ministry for the Economy and Competitiveness (MINECO) and Junta de Castilla y León.

Wissenschaftliche Ansprechpartner:

Prof. Dr. Olaf Stemmann
Chair of Genetics
University of Bayreuth
Phone: +49 (0)921 / 55-2701
E-Mail: olaf.stemmann@uni-bayreuth.de

Originalpublikation:

Susanne Hellmuth, Laura Gómez-H, Alberto M. Pendás, Olaf Stemmann: Securin-independent regulation of separase by checkpoint-induced shugoshin-Mad2. Nature (2020), doi: https://dx.doi.org/10.1038/s41586-020-2187-y

Christian Wißler | Universität Bayreuth
Further information:
http://www.uni-bayreuth.de/

More articles from Life Sciences:

nachricht Drug discovery: First rational strategy to find molecular glue degraders
03.08.2020 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

nachricht Chlamydia: Greedy for Glutamine
03.08.2020 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: TU Graz Researchers synthesize nanoparticles tailored for special applications

“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.

Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...

Im Focus: Tailored light inspired by nature

An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.

Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...

Im Focus: NYUAD astrophysicist investigates the possibility of life below the surface of Mars

  • A rover expected to explore below the surface of Mars in 2022 has the potential to provide more insights
  • The findings published in Scientific Reports, Springer Nature suggests the presence of traces of water on Mars, raising the question of the possibility of a life-supporting environment

Although no life has been detected on the Martian surface, a new study from astrophysicist and research scientist at the Center for Space Science at NYU Abu...

Im Focus: Manipulating non-magnetic atoms in a chromium halide enables tuning of magnetic properties

New approach creates synthetic layered magnets with unprecedented level of control over their magnetic properties

The magnetic properties of a chromium halide can be tuned by manipulating the non-magnetic atoms in the material, a team, led by Boston College researchers,...

Im Focus: A new method to significantly increase the range and stability of optical tweezers

Scientists of Tomsk Polytechnic University jointly with a team of the V.E. Zuev Institute of Atmospheric Optics of the Siberian Branch of the Russian Academy of Sciences have discovered a method to increase the operation range of optical traps also known

Optical tweezers are a device which uses a laser beam to move micron-sized objects such as living cells, proteins, and molecules. In 2018, the American...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“Conference on Laser Polishing – LaP 2020”: The final touches for surfaces

23.07.2020 | Event News

Conference radar for cybersecurity

21.07.2020 | Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

 
Latest News

Novel approach improves graphene-based supercapacitors

03.08.2020 | Information Technology

Germany-wide rainfall measurements by utilizing the mobile network

03.08.2020 | Information Technology

Drug discovery: First rational strategy to find molecular glue degraders

03.08.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>