Guest Editors
Chris Toseland
University of Sheffield
Chris Toseland is a Senior Lecturer/Associate Professor at the University of Sheffield in the Department of Oncology and Metabolism. His research group is interested in nuclear organisation with respect to transcription and DNA repair. The lab specializes in the application of fluorescence and mechanical measurements from whole cells to single molecules. He received a BSc Biochemistry degree from the University of Wales – Aberystwyth in 2006 then commenced a PhD at the MRC National Institute for Medical Research/University of London. His thesis focused upon the biochemical and biophysical characterisation of DNA helicases. At the end of his PhD, he was awarded an EMBO Long Term Fellowship to move to the LMU–Munich to work on single molecule studies with myosin motors. After 3 years, he relocated to the Max Planck Institute of Biochemistry with a research focus on genome organisation. He then established his research group at the University of Kent in 2015.
Ália dos Santos
University of Sheffield
Ália dos Santos is currently a PhD student in the lab of Dr. Christopher Toseland, at the Department of Oncology and Metabolism at the University of Sheffield. Ália received her BSc in Biochemistry from the University of Lisbon in 2012. Following this, Ália worked in glycobiology at Imperial College London for Prof. Kurt Drickamer and then at King’s College London in membrane protein stability with Prof. Paula Booth. For her doctoral work, Ália’s research has focused on the effects of DNA damage on the mechanical properties of the nucleus. Ália is also interested in the role of molecular motors in transcription and has a special interest in super-resolution microscopy and atomic force microscopy.
Collection Overview
The eukaryotic genome is continuously attacked by multiple factors causing DNA lesions. This includes ultraviolet light, and intracellular reactive oxygen species. This leads to alterations in the DNA structure, ranging from DNA base modifications through to double-strand breaks.
Eukaryotic cells have evolved genome repair and surveillance mechanisms to specifically respond to the form of DNA damage. These fall under the pathways of base excision, nuclear excision, homology-directed and DNA mismatch repair, along with non-homologous end joining, amongst others. These pathways respond to the damage, regulate the cell cycle, alter chromatin, and enable repair.
This Collection summarizes a variety of established methods, and highlights novel and emerging techniques, relating to single molecule methodologies. These approaches provide quantitative insights into the dynamics and organization of biomolecules during DNA damage and throughout the DNA repair process. These methods can range from single molecule tracking of DNA repair proteins, force spectroscopy measurements on the cell nucleus during DNA damage, through to in vitro magnetic tweezer-based assays measuring protein-DNA interactions. These methods reveal the molecular details underpinning the DNA damage response, so that we can understand the onset of diseases such as cancer. Moreover, this will help develop therapeutic interventions targeting these processes.
Example areas to be included in this Collection are: (1) DNA labelling and imaging techniques, (2) imaging protein organisation and dynamics, (3) mechanical measurements on whole cells, and (4) in vitro mechanical and single molecule measurements.
