Department Molecular Genetics
Principal investigator Alex Pines
E-mail address a.pines@erasmusmc.nl
Website https://www.erasmusmc.nl/en/research/researchers/pines-alex
Transcription interfering lesions
Supervisor: Alex Pines, a.pines@erasmusmc.nl
Recent evidence suggests that persistent DNA damage is associated with ageing and development of neurodegenerative diseases. DNA is susceptible to acquire damage by environmental chemicals, solar radiation and, strikingly, also by molecules produced by the cell’s own metabolism. It was shown that particularly persistent DNA damage that interferes with gene transcription is an important driver of age-related diseases, including progressive neurodegeneration. To counteract the harmful effects of these so-called Transcription-Interfering Lesions (TILs), cells have evolved DNA Damage Response (DDR) that coordinates key cellular processes, including several DNA repair pathways, via post-translational protein modifications (PTMs). The goal of Pines’ research is to reveal the molecular details of DDR to fully comprehend the root causes of TILs driving progressive neurodegeneration.
Techniques
Recent advances in contemporary experimental approaches, such as sophisticated live cell imaging, CRISPR-mediated genome editing, and genome-wide omics have set the scene to take up this challenging research objectives
Further reading
The small CRL4CSA ubiquitin ligase component DDA1 regulates transcription-coupled repair dynamics
Live cell transcription-coupled nucleotide excision repair dynamics revisited