Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dance of the RNases: Coordinating the removal of RNA-DNA hybrids

28.11.2019

Research teams have deciphered how two enzymes are coordinated to remove RNA-DNA hybrid structures from chromosomes

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.


S restricted expression and G2/M restricted expression.

Credit: ill./©: IMB

RNA-DNA hybrids are important for promoting normal cell activities like gene regulation and DNA repair, but having too many is also a risk for DNA damage and can lead to neurodegenerative disease and cancer. In their article, which was published today in Cell Reports, Brian and Helle show that the enzyme RNase H2 removes RNA-DNA hybrids primarily after DNA replication. Any remaining RNA-DNA structures are then removed by RNase H1, which acts independently of cell cycling.

DNA is normally found as a stable, double-stranded structure. However, DNA also sometimes interacts with RNA to form RNA-DNA hybrid structures that regulate gene expression and DNA repair. R-loops are a special type of RNA-DNA hybrid in which an RNA strand binds to one strand of a DNA molecule and pushes out the other DNA strand so that it is exposed as a single-stranded loop. R-loops can regulate gene activity, but also quickly become dangerous because incorrect removal can damage the DNA, potentially causing mutations. Therefore, excess R-loop formation can be toxic for cells - indeed, mutations in R-loop removal proteins are known to contribute to neuroinflammatory diseases and cancer.

R-loop removal is catalysed by the enzymes RNase H1 and RNase H2, which degrade the RNA strand. In addition, RNase H2 also has a secondary ability to excise single ribonucleotides, which can sometimes be mistakenly incorporated into DNA by polymerases in a process known as ribonucleotide excision repair (RER). Previous studies showed that mutation of RNase H2 disrupted genome stability more than RNase H1 mutation, suggesting that RNase H2 has a more important role in maintaining genome stability. However, it was never fully understood how these important enzymes are coordinated.

To dissect the distinct roles of RNase H1 and H2 in R-loop removal, the Luke lab engineered yeast to express RNase H1 and H2 only during specific phases of the cell cycle and then exposed them to methyl methanesulfonate (MMS), an agent that increases R-loop formation. Only yeast that could effectively remove R-loops would survive, while those with impaired R-loop removal would not survive.

With support from the Ulrich lab, they found that yeast expressing RNase H2 exclusively during G2 (the 'growth phase' of the cell cycle following DNA replication) were resistant to MMS, whereas yeast expressing RNase H2 only during S phase (the DNA replication phase) were more sensitive. This suggested that RNase H2 primarily acts to process R-loops during G2. In contrast, yeast expressing RNase H1 in either G2 or S phase were both able to survive in MMS. Surprisingly, RNase H2 expression in S phase actually induced more DNA damage, 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.

These results may explain why cells have evolved two different RNAse H enzymes. Brian Luke clarifies: "We think that RNase H2 is the 'housekeeping' enzyme that repairs the majority of RNA-DNA hybrids, but it is strictly regulated by cell cycling and acts only in G2 phase, or after DNA replication." Brian and Helle speculate this may be because the additional RER activity of RNase H2 creates nicks in the DNA, which are a risk for double-strand breaks during DNA replication in S phase. Therefore, cells may have also evolved a secondary enzyme, RNase H1, which does not have RER activity and can act in all phases of the cell cycle, including S phase.

These findings help us to further understand how cells repair DNA damage associated with RNA-DNA hybrids and how impairment of this process contributes to disease.

Media Contact

Ralf Dahm
press@imb.de
49-061-313-921-455

 @uni_mainz_eng

http://www.uni-mainz.de 

Ralf Dahm | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

Further reports about: DNA DNA damage DNA repair DNA replication RNA RNA-DNA RNase activity enzyme enzymes

More articles from Life Sciences:

nachricht New yeast species discovered in Braunschweig, Germany
13.12.2019 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

nachricht Saliva test shows promise for earlier and easier detection of mouth and throat cancer
13.12.2019 | Elsevier

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Virus multiplication in 3D

Vaccinia viruses serve as a vaccine against human smallpox and as the basis of new cancer therapies. Two studies now provide fascinating insights into their unusual propagation strategy at the atomic level.

For viruses to multiply, they usually need the support of the cells they infect. In many cases, only in their host’s nucleus can they find the machines,...

Im Focus: Cheers! Maxwell's electromagnetism extended to smaller scales

More than one hundred and fifty years have passed since the publication of James Clerk Maxwell's "A Dynamical Theory of the Electromagnetic Field" (1865). What would our lives be without this publication?

It is difficult to imagine, as this treatise revolutionized our fundamental understanding of electric fields, magnetic fields, and light. The twenty original...

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Supporting structures of wind turbines contribute to wind farm blockage effect

13.12.2019 | Physics and Astronomy

Chinese team makes nanoscopy breakthrough

13.12.2019 | Physics and Astronomy

Tiny quantum sensors watch materials transform under pressure

13.12.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>