SciLifeLab seminar series-Campus Solna, Marcel Tijsterman, Mutational signatures and scars by DNA Repair

Tuesday January 29th at 10:00

Prof. Marcel Tijsterman

Marcel Tijsterman studied Chemistry at the Leiden University, specializing in Molecular Genetics. He received his PhD in 1999 studying “Repair analysis of UV-induced DNA damage at nucleotide resolution”. For his postdoctoral work, he joined the lab of Ronald Plasterk at the Netherlands Cancer Institute in Amsterdam, which moved to the Hubrecht Institute in Utrecht in 2001. There he started his independent research on genomic instability and DNA damage responses. In 2009, he moved his research group to the Leiden University Medical Center (LUMC), where he was appointed professor in 2014. The title of his inaugural lecture was: “On Darwin and DNA, and on beauty in decay”. In 2017, he was also appointed professor of Genome Engineering at the Institute of Biology Leiden (IBL)

Genome stability is essential to accurately transmit genetic information to progeny, maintain tissue homeostasis and prevent disease. Unfortunately, all of us (either personally, or in the people surrounding us) will experience the fact that copying and/or repairing our DNA does not occur without error. Mutations will accumulate during our lifetime and cause the disease that is responsible for a quarter of all deaths in the Western world: cancer.

Tijsterman’s research focuses on understanding and exploiting mechanisms that fuel genome instability. His lab has particular interest in how cells deal with obstacles to DNA replication, such as thermodynamically stable secondary DNA structures (e.g. G-quadruplexes) and damaged DNA bases. These obstacles can lead to chromosomal breaks, which when left unrepaired cause cell death and/or aneuploidy, but in case of inaccurate repair drive carcinogenesis. Using C. elegans as a model system, the Tijsterman laboratory discovered that cells employ an alternative mechanism to repair DNA breaks that result from replication impediments, which they termed Theta-Mediated End Joining (TMEJ), as it critically depends on the functionality of the A-family polymerase Theta (Koole et al., Nature Commun. 2014; Roerink et al., Genome Res. 2014; Lemmens et al., Nature Commun. 2105; van Schendel et al., PLOS Genet. 2016). TMEJ repairs CRISPR-induced DNA breaks in worms and mammalian cells, leading to specific genomic scars that are also observed in congenital disease alleles (van Schendel et al., Nature Commun. 2015; Schimmel et al., EMBO J. 2017). TMEJ is also a key driver of random integration of DNA, a phenomenon also known as illegitimate recombination, in both mammalian cells as well as in plants (Van Kregten et al., Nature Plants 2016, Zelensky et al., Nature Commun. 2017). As such, Dr. Tijsterman serendipitously identified the mechanism that underlies transgenesis in plants, which will be further studied at the Institute Biology Leiden (IBL), in the context of genome engineering strategies to benefit plant biotechnology and crop development. While the primary aim of his research is to provide mechanistic insight into the processes that drive genome instability and cancer development, he aims to use this knowledge to develop clinically relevant applications such as gene-correction methods and targeted cancer therapies.

Host: Bennie Lemmens;

Read more about Marcel Tijsterman´s research