As part of an active scientific community that studies the DNA damage response (DDR) and its impact on cancer and aging, research in the lab of Matthias Altmeyer is aimed at elucidating cellular mechanisms of genome integrity maintenance and their deregulation in human disease. Here you can explore who we are and what we do. Welcome!
Review on DNA Repair and Mechanobiology
Out in Chromosoma. Topics include cell cycle regulation & DNA replication, replication stress & chromosome fragility, telomere maintenance & ALT, emerging links between repair condensates and the nuclear cytoskeleton.
In a recent publication we found that the essential replication protein A (RPA) self-interacts and forms dynamic non-stoichiometric condensates with ssDNA, regulated by phosphorylation of an IDR.
Motivated applications from postdoc candidates with a strong interest in genome stability and willing to apply for fellowships are always encouraged. PhD students are recruited through the Life Science Zurich Graduate School.
Sandhya Manohar starts her research program on big cells at our department
Sandhya Manohar joins us from ETH to set up her research program on implications of cell size on mammalian genome homeostasis. Supported by the SNSF Ambizione Career Development Program, Sandhya will investigate how cells sense their own enlargement and how changes in cell size affect cell cycle commitment and genome integrity.
Phase separation properties of RPA combine high-affinity ssDNA binding with dynamic condensate functions at telomeres
RPA binds ssDNA with sub-nanomolar affinity. Vincent found that, despite their ultra-high affinity for one another, RPA and ssDNA form dynamic non-stoichiometric condensates, which are regulated by phosphorylation and help to coordinate telomere recombination in cancer cells. Published in NSMB
Aleksandra’s paper is out in Nature Communications
June 2021
RPA shields inherited DNA lesions for post-mitotic DNA synthesis
Fragile genomic regions undergo mitotic DNA synthesis (MiDAS). Aleksandra found evidence for post-mitotic DNA synthesis (post-MiDAS). Post-MiDAS occurs at telomeres, particularly in ALT-positive cancer cells, and is amplified by replication stress. Published in Nature Communications.
CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks
From a close collaboration with the lab of Haico van Attikum, and with great help from the labs of Sébastien Huet, Alfred Vertegaal, Jessica Downs and Martijn Luijsterburg, the chromatin remodeler CHD7 emerged as an early responder to DNA damage to regulate chromatin dynamics around DNA break sites and initiate repair. Finally out in Nature Communications.
Marco’s paper on TRIP12-regulated PARP inhibitor efficiency is out
August 2020
The ubiquitin ligase TRIP12 limits PARP1 trapping and constrains PARP inhibitor efficiency
We found that the ubiquitin E3 ligase TRIP12, through its PAR-binding WWE domain, targets PARP1 for proteasomal degradation, affecting PARP functions and PARP inhibitor efficiency. Congratulations to Marco and big thanks to our collaborators Qingyao Huang and Michael Baudis for their help. Published in Cell Reports.