Understanding of the mechanism of communication along DNA: When cells divide, DNA is replicated so that each new cell receives a complete copy of parental genomic information. Copy errors have to be repaired to avoid mutations which might otherwise increase the risk to develop cancer. During this repair process, the protein molecules that carry out the different reaction steps have to communicate between different sites on DNA. The consortium has established that the repair proteins move along the DNA backbone during this search process, and that obstacles on the DNA can be bypassed during this search. This work has been published.
The protein that recognizes the replication error, MutS, has to recognize this error, bind to it and only then recruit the next protein in the repair cascade. During this process MutS changes shape multiple times. Using a high resolution technique called cryo-electron microscopy, the consortium has taken snapshots of these different states, which give unprecedented detail and explain how MutS does its important job.
Understanding which proteins collaborate at which reactions steps and how they do this: During the DNA repair process, many proteins collaborate to 1) find copy errors or damage in the DNA, 2) recruit partner proteins that can remove the error or damage, and 3) recruit proteins that can restore the original information. In order to understand the molecular mechanism of these processes, the consortium has designed new reagents, assays and technologies. These are used to study the mechanism of the repair processes in detail.
The training program: The training program is an essential and central component of DNARepairMan. The consortium has organized four scientific workshops, which have been attended by all the fellows as well as several researchers from outside the consortium. The workshops entailed ‘Protein Structure Analysis’, ‘Advanced single molecule analysis’, ‘Fluorescence and cross linking approaches’ and 'Hybrid structural biology. Fellows have also received entrepreneurship coaching sessions to prepare them for a putative career as entrepreneur, a lecture on Research Ethics, as well as other transferable skills and a career event.
DNARepairMan is a truly interactive consortium; all the young researchers have already spend prolonged research visits (secondments) in each other’s laboratories to learn new techniques and to collect data.
A unique component of DNARepairMan is the active collaboration with the Art Academy in Rotterdam (de Willem de Kooning Akademy). Through an intensive program including the DNArepairMan fellows, scientists, students and teachers from the Art Academy and the Erasmus MC, the consortium is exploring new ways and means to communicate scientific topics and results as well as the importance of fundamental science in general to society. This has resulted in several short animations about the scientific projects and the importance of science in general.
