Friend or Foe: Transcription and RNA Meet DNA Replication and Repair

Event Report by Apoorva Baluapuri, University of Würzburg, Germany

RNA and DNA were first described by the Swiss biologist Friedrich Miescher in 1868. About 150 years later, we stand at crossroads of the two disciplines which have arisen as a result of dedicated research on both molecules. The first EMBL symposium on the connections between transcription and DNA replication/repair research was a major step forward in combining the progress from wide ranging topics, thus generating a consensus on how gene expression and DNA transactions cooperate.

The symposium, which was the second one from EMBL this year,  was scheduled just a day after International Women’s Day, and that aligned very well with the equally represented line-up of speakers and organisers!

The titular opening session was dedicated to transcription-associated genomic instability where all aspects of R-loops and ribonucleotide excision repair in transcription coupled DNA double strand break repair were covered. For example, Gaëlle Legube (CNRS – University of Toulouse, France) expanded in great detail on the influence of DSB-induced chromatin conformation and the strong potential of 3C-based technologies, while Elodie Hatchi (Dana Farber Cancer Institute, Boston, USA) explained about her recent publication in Nature concerning the impact of BRCA1, RAD52 and PALB2 on small RNA-driven DNA repair.

Eventually, we switched over to a more translational theme with Rushad Pavri (IMP, Vienna, Austria) who spoke about the relation between DNA replication timing and frequency of oncogenic translocations.

This time around, the poster presentation sessions were equally dynamic with topics being covered from role of RBMX in RNA processing (Sara Luzzi, University of Newcastle) to role of MYCN in reconciling elevated transcription levels with DNA replication (Dimitrios Papadopoulos, University of Würzburg, Germany).

To end the first day, Philippe Pasero (CNRS, France) tried to answer the old question of the chicken or the egg in terms of toxic R-loops, if they are the cause or consequences of DNA replication stress, while Andrew Deans (St. Vincent’s Institute of Medical Research, Australia) explained about fork re-modellers as a general mechanism of R-loop removal.

The second day started out on a high note by a talk on the consequences of DNA damage and heat shock on Pol II from Jesper Svejstrup. Prof Svejstrup recently moved his lab from the Francis Crick Institute in London to the University of Copenhagen (Faculty of Health and Medical Sciences).

To make things even more exciting at the symposium, Martin Eilers (University of Würzburg, Germany) spoke about conflict resolution by MYCN between “friends and foes”, i.e. Pol II and replication fork. This was followed by talk by Marco Foiani (University of Milan, Italy) who showed the role of ATR in nuclear integrity.

In between the breaks, the participants eagerly shared their setup of how they were joining the virtual conference:

Not only were the home setups on display, but we also got a glimpse of “add-on” participants at the conference:

Along with this fun, the second day’s poster session continued with equally interesting topics as the previous day. The virtual conference platform provided by Engagez came across as a handy tool in coming as close as possible to the in-person poster presentations.

Frédéric Chédin (University of California, Davis, USA) closed the day by talking about interplay between splicing and R-loops.

In the next two days, a wide variety of topics and methods were covered. For example,  Nick Proudfoot (University of Oxford, UK) dazzled with correlation between R-loops and antisense transcription while Petra Beli (IMB, Mainz, Germany) moved the focus from genomics to proteomics with èlan. She spoke about a method called “RDProx” which maps R-loop proximal proteome in a native chromatin environment.

Also, junior group leaders like Marco Saponaro (University of Birmingham, UK) answered what happens to replication when it encounters transcription and Madzia Crossley (Stanford University, USA) showed CytoDRIP-blots to probe RNA-DNA hybrids on gels which showed that SETX and BRCA1 loss, along with splicing inhibition, results accumulation of RNA-DNA hybrids in cytoplasm!

All along the talks, whichever questions (which, by the way, were in majority from younger researchers) didn’t get answered, were posted and responded to in the “Forum” section: this actually became a valuable summary of quite a few topics.

The networking options were also in abundance, be it the Virtual Bar mixer, or Meet the Editors session on the online platform. Given that editors from elite journals like EMBO, PLoS Biology etc. were present, it gave a nice opportunity for the researchers to gauge where their next big story could find a good home.

In summary, the symposium gave the feeling of being cozy without being too small and specific in terms of the topics covered, and benefited both the experienced and young researchers in an equal way. It was a common understanding and expectation among the participants that this symposium would perhaps be held in person next time if possible.

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