IMB-Mainz/news News en IMB-Mainz/news 18 16 News TYPO3 - get.content.right Wed, 27 Nov 2019 09:33:26 +0100 Dance of the RNases: coordinating the removal of RNA-DNA hybrids For more information click here Two research teams led by Professors Brian Luke and Helle Ulrich at the Institute of Molecular Biology have deciphered how two enzymes, RNase H2 and RNase H1, are coordinated to remove RNA-DNA hybrid structures from chromosomes. In their article, which was published today in Cell Reports, Brian and Helle show that RNase H2 removes RNA-DNA hybrids after DNA replication, and then any remaining RNA-DNA structures are removed by RNase H1, which acts independently of cell cycling. DNA also sometimes interacts with RNA to form RNA-DNA hybrid structures called R-loops that regulate gene expression and DNA repair. However, having too many is also a risk for DNA damage and can lead to neurodegenerative disease and cancer. R-loop removal is catalysed by the enzymes RNase H1 and RNase H2. However, it was never fully understood how these important enzymes are coordinated. In their study, the Luke lab dissected the distinct roles of RNase H1 and H2 by engineering yeast to express either RNase H1 or H2 only during specific phases of the cell cycle and then testing their ability to remove R-loops. With support from the Ulrich lab, they show that RNase H2 primarily acts to process R-loops during G2, while RNase H1 is able to remove R-loops in either G2 or S phase. Surprisingly, RNase H2 actually induced more DNA damage in S phase, which required a special type of DNA repair called homologous recombination to fix. This pathway was not previously known to act during S phase. Therefore, this study may have revealed an unexplored repair pathway which counters damage caused by RNase H2 activity during DNA replication. For the full press release, please click




Homepage News & Events Wed, 27 Nov 2019 09:33:26 +0100
The poly(A) detector: how cells avoid making toxic proteins For more information click here Researchers at the Institute of Molecular Biology (IMB) in Mainz, Germany have discovered a new route used by cells to avoid making defective proteins. In their paper published in Genome Biology, the research groups led by Dr Petra Beli and Dr Julian König show how MKRN1 acts as a sensor for detecting abnormal mRNAs and blocks them from being translated into aberrant proteins that can be toxic to the cell.

Proteins are the building blocks of cells and must be constantly produced. However, the protein production process needs to be tightly controlled as there are many chances for mistakes. One crucial step of protein production is mRNA polyadenylation, when the mRNA is cleaved and a long row of adenosines, called a poly(A) tail, is added.

Sometimes the mRNA is mistakenly cut early in its sequence and the poly(A) tail is added to the now shortened mRNA. This is called premature polyadenylation. Translation of these shortened mRNAs creates non-functional proteins that can form toxic aggregates and contribute to neurodegenerative disease.

To prevent this, cells have an in-built quality control mechanism that detects faulty mRNAs and stops ribosomes from translating them. However, until now scientists did not know how premature poly(A) sequences are recognised and how they stop translation.

In a joint study, the research groups of Petra Beli and Julian König (IMB) along with Kathi Zarnack (Goethe University Frankfurt) show that Makorin Ring Finger Protein 1 (MKRN1) binds to and is essential for stopping translation at poly(A) sequences. MKRN1 may therefore act as a sensor allowing the cell to detect faulty mRNAs with premature poly(A) tails and stop their translation as early as possible.

For the full press release, click here.

Homepage News & Events Wed, 23 Oct 2019 16:32:45 +0200
Dividing cells fix damaged DNA in nuclear PORTs For more information click here The research group lead by Professor Helle Ulrich at the Institute of Molecular Biology (IMB) in Mainz, Germany has made a breakthrough discovery in how cells repair damaged DNA during replication. In an article published today in Molecular Cell, they show that damaged DNA is repaired in specialised areas of the nucleus, which they named ‘postreplicative repair territories’, or PORTs.

DNA is frequently exposed to damaging agents that chemically modify its bases, creating DNA lesions. Scientists had assumed that these lesions are repaired in DNA repair centres at the periphery of the cell nucleus. However, it was unclear how cells coordinated this repair with DNA replication.

In their latest study, Prof. Ulrich and her colleagues investigated how and where DNA lesions are repaired during replication by labelling Replication Protein A (RPA), a protein which binds to DNA that is actively undergoing repair, with a fluorescent marker. They then monitored the fluorescent RPA signal in dividing yeast cells treated with a drug that induces DNA lesions. Surprisingly, they found that DNA lesions are repaired in defined areas within the nucleus, rather than at the nuclear periphery, and only after the DNA had been replicated. Prof. Ulrich and her team named these repair regions ‘postreplicative repair territories’, or PORTs.

This finding shows that cells keep their DNA repair machinery well away from replication machinery and advances our understanding of how cells cope with damaged DNA during replication. Understanding how DNA lesions are repaired could also provide a mechanistic basis on which new anti-cancer drug therapies could be designed in the future.

For the full press release, click here.

Homepage News & Events Fri, 11 Oct 2019 10:52:13 +0200
IPP's Winter Call 2019 is now OPEN! Apply by 19 Nov. For more information click here  

Mon, 07 Oct 2019 13:42:43 +0200
Breaking bad: How breaks in folded, active DNA promote leukaemia in response to cancer therapy For more information click here Cancer is one of the most prevalent diseases worldwide, with the World Health Organisation estimating 18.1 million new cases in 2018. The predominant method for fighting cancer is chemotherapy - introducing a toxic substance to the body that preferentially kills cancer cells. However, chemotherapy can also cause severe complications. One of the worst is the development of a second cancer, usually leukaemia. New research published in Molecular Cell from the group of Vassilis Roukos at the Institute of Molecular Biology (IMB) in Mainz unveils how these treatment-related cancers can arise. 

Cancers are commonly treated with anticancer drugs called topoisomerase poisons. Unfortunately, treatment with topoisomerase poisons can also cause DNA rearrangements (translocations) in healthy cells that disrupt gene regulation and lead to the development of leukaemia. However, it was unclear why these leukaemia-promoting translocations are so common after treatment with topoisomerase poisons.

In their work published in the latest issue of Molecular Cell, Dr Vassilis Roukos and his group, together with the lab of Argyris Papantonis (Center for Molecular Medicine Cologne) and the lab of Nicola Crosetto (Karolinska Institute, Stockholm), combined cutting-edge genomics and single-cell imaging methods to determine why these leukaemia-promoting translocations arise. They found that certain sites with highly active genes tend to be close to regions of DNA folding that are under more mechanical strain. This makes them susceptible to DNA breaks caused by topoisomerase poisons, producing translocations that drive leukaemia.

This finding highlights how gene activity and the arrangement of DNA within the nucleus can have a profound impact on events that trigger genomic instability to promote cancer.

For the full press release, click here.

Thu, 13 Jun 2019 14:30:00 +0200
Peter Baumann elected as EMBO member For more information click here Professor Peter Baumann has been elected as an EMBO Member, joining a group of more than 1,800 top researchers in Europe and around the world.

EMBO Members are selected by the Council of EMBO (European Molecular Biology Organization) for research at the forefront of the life sciences. This year, 56 new EMBO Members were elected from 22 countries. As an EMBO member, Prof. Baumann will serve on the EMBO Council, evaluate EMBO funding applications, and help mentor the next generation of young scientists.

For the full press release, please click here.

Wed, 12 Jun 2019 12:54:07 +0200
Keeping the neighbours quiet: A lesson from C. elegans in using what you have to hand For more information click here Researchers from the Institute of Molecular Biology (IMB) in Mainz have uncovered a new evolutionary origin for the anti-parasitic genome defence system, piRNAs, in worms. In their research paper published in Genes and Development, the group of Prof. René Ketting describe how the piRNA pathway in C.elegans developed out of a more ancient, evolutionarily conserved protein system that is needed for correct gene expression.

While studying the piRNA system in the small nematode C. elegans, the group discovered a new protein complex essential for their production, which they called PETISCO -tapas in Portuguese. This protein complex appears to have two distinct functions, flavours, that are determined by its interaction partners, PID-1 and TOST-1. PID-1, in evolutionary terms a relatively young protein, uses PETISCO to make piRNAs, while TOST-1, a genetically older protein, has a gene expression function. While TOST-1’s function still needs to be molecularly defined, it appears to be involved in producing small RNA molecules needed to join gene segments together to create a functional transcript. The results strongly suggest that this latter, essential PETISCO system has been coopted later during C. elegans’ evolutionary history to produce piRNAs. Indeed, this new finding highlights how evolution can build on existing structures to derive novel effective parasite-control systems.

For the full press release click here.

Mon, 03 Jun 2019 16:42:16 +0200
DFG funds a Research Training Group on Gene Regulation in Evolution "GenEvo" at JGU and IMB For more information click here The German Research Foundation (DFG) has approved the establishment of the “GenEvo – Gene Regulation in Evolution: From Molecular to Extended Phenotypes” Research Training Group (RTG) at the Faculty of Biology at Johannes Gutenberg University Mainz (JGU) with effect from July 2019. This RTG, working in cooperation with the Institute of Molecular Biology (IMB), will offer a structured, high-calibre research and training program enabling its PhD students to acquire interdisciplinary qualifications and obtain autonomy at an early stage of their scientific careers. The scientific objective of GenEvo is to gain a better understanding of the evolution of complex and multi-layered genetic regulation systems. The DFG will provide some EUR 5 million to the RTG over the first funding period of four and a half years, plus another EUR 1 million in overhead funding to bolster the strategic orientation of the university.

For the full press release click here

For more information on GenEvo click here

Mon, 20 May 2019 14:29:07 +0200
2019 IMB Conference "Chromosome Territories & Nuclear Architecture" Registration is still available. Click here  

Thu, 02 May 2019 15:40:23 +0200
Joan Barau joins IMB as a junior group leader For more information click here The Institute of Molecular Biology (IMB) is delighted to welcome Dr Joan Barau as a Junior Group Leader. Dr Barau investigates how the epigenetics of the germ cell lineage and intragenomic conflict impact mammalian fertility.

The blueprint for every living organism on Earth is coded into its genome in the form of DNA and made manifest through the activity of genes. Indeed, each genome can be viewed as its own environment. This environment is populated by genes whose specific behaviour gives each cell its own identity. Like any environment, a genome is subject to outside disruption, particularly through genetic parasites. These are chunks of foreign DNA that exploit a genome’s replication ability without giving any direct benefit to the cell or organism as a whole. This is particularly relevant for the genomes of cells involved in reproduction. Genetic parasites and their activity within a genome can threaten its stability and thus its ability to be inherited correctly by offspring.

These parasites – known as transposons – are prolific: more than 50% of a human’s genome derives from them. Transposons have the ability to move within a genome, hence their name. They maintain their presence not through their usefulness but through over-replication and increasing copy numbers. This disruptive invasion and increasing genetic burden does not go unchallenged. Genomes fight back through selection for mechanisms that allow the suppression and elimination of parasitic DNA. This self-propagating conflict has been shaping the sequence and structure of genomes for billions of years. It also provides fertile ground for the evolution of novel mechanisms of genome regulation that play essential roles in normal and pathological development.

In joining IMB, Dr Barau will bring his expertise in the various mechanisms genomes use to counteract the presence of transposons. His group will continue to investigate new mechanisms of transposon regulation at all levels of cell and organismal biology. In particular studying how and if these mechanisms are repurposed during normal and pathological development in mammals. As Dr Barau explains, “because the germ cell lineage represents a hotspot of transposon activity, our group will maintain a strong focus into germ cells and early embryos. We will also expand to other relevant physiological contexts including examples of their involvement in development, gene regulation and disease.”

Dr Barau explains he will focus on how mammals use classical modifications to DNA (epigenetic) to properly regulate the production of genomes in gamete cells while at the same time keeping transposons in check. “Cytosine methylation is a widespread epigenetic modification that mammalian genomes use to repress transposons and it has a crucial role for germline development and fertility. We are very interested in understanding how cells reprogramme this mark during gamete cell production ensuring it is absent from germline genes but placed back selectively at transposons. While scientists have known for over ten years that small RNAs are involved, the precise mechanisms and proteins behind this mechanism are still poorly understood.”

A PDF version of the press release can be found here

Wed, 03 Apr 2019 10:11:18 +0200