Before a cell divides, it must first handle a large-scale project: Its entire genetic material has to be duplicated so that each of the two daughter cells is equipped with a full copy after cell division. As errors in this DNA replication could lead to the death of the cell, the process is rigorously controlled. It takes place in two phases. Researchers at the Max Planck Institute of Biochemistry in Martinsried have now revealed in the journal Cell Reports that these two phases are strictly separated from one another by breaks, thereby preventing errors in the DNA replication.
large-scale projects are frequently susceptible to errors and these are generally very cost-intensive. A cell’s most important large-scale project is the replication of its DNA, i.e. the complete duplication of its genetic material. Here, errors such as the inadvertent multiplication of a DNA sequence can change the structure of the chromosomes.
This can lead to cell death or, in the case of multi-cellular organisms such as humans, to the development of cancer. For this highly important project, the cell increases its success rate by dividing the process of DNA replication into a planning phase, known as the “licensing” phase, and an implementation phase, known as the “firing” phase.
The two phases follow in sequence. Boris Pfander, head of the “DNA Replication and Genome Integrity” research group, and his team have demonstrated that the baker’s yeast S. cerevisiae separates the timing of these phases from one another and that the Sld2 protein plays an important role in this regulation.
“A crucial factor in the success of the DNA duplication project is, on the one hand, that project planning is completed before the building work begins, but also that no new plans are made while the actual building work is being carried out,” Pfander explains.
The Martinsried-based team has shown that the cell, at the transition between the implementation phase and the next planning phase, first switches off all building machines (firing factors) – first and foremost, the Sld2 building machine. The correct time for switching off Sld2 is determined by four different kinase enzymes called CDK, DDK, Mck1 and Cdc5, which mark Sld2 with phosphate molecules. When all four enzymes have phosphorylated Sld2, the enzymes Dma1 and Dma2 become active and ultimately switch off Sld2.
If Sld2 is not switched off on time, the cell loses some of its valuable break time. In these circumstances, the DNA can still reliably duplicate, but it is vulnerable to the occurrence of sporadic errors. This means that it is not only important that cells take breaks, but that the length of these breaks is sufficient. “We now want to look for similar important breaks in other multi-cellular organisms,” says Pfander. “The division of the firing and licensing phase helps to counteract genomic defects. We can imagine that cancer cells do not take sufficient breaks, and that our research will help gain a better understanding of the development of cancer.”
K.-U. Reusswig, F. Zimmermann, L. Galanti and B. Pfander: Robust replication control is generated by temporal gaps between licensing and firing phases and depends on degradation of firing factor Sld2. Cell Reports, October 2016
Dr. Boris Pfander
DNA Replication and Genome Integrity
Max-Planck-Institute of Biochemistry
Am Klopferspitz 18
Dr. Christiane Menzfeld
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Tel. +49 89 8578-2824
http://www.biochem.mpg.de/en/news - More press releases of the MPI of Biochemistry
http://www.biochem.mpg.de/pfander - Website of the Research Group "DNA Replication and Genome Integrity" (Boris Pfander)
Dr. Christiane Menzfeld | Max-Planck-Institut für Biochemie
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Earth Sciences
05.12.2016 | Physics and Astronomy
05.12.2016 | Life Sciences