Impact of Endogenous Genomic Damage on Adult Stem Cells and Tissue Homeostasis
Invloed van DNA schade en reparatie op adulte stamcellen en weefselhomeostase
We present important findings linking DNA repair pathways with stem cell exhaustion during ageing, as well as in specific cancer-related mutational patterns. Moreover, we put forward a general model, in which remaining cellular lifespan determines which DNA damage response strategy is used by the cell.
Such a model provides an explanation for the segmental ageing phenotypes of human progeroid syndromes and DNA repair-deficient corresponding mouse mutants, as well as the different aging trajectories between organs and tissues during natural ageing.
|Keywords||DNA damage, DNA repair, Adult Stem Cells, small intestine, liver, organoids, ERCC1, Nucleotide Excision Repair, cellular lifespan, anti-ageing strategy, cancer, mutational signature, DNA damage tolerance, REV1|
|Promotor||J.H.J. Hoeijmakers (Jan) , J. Pothof (Joris)|
|Publisher||Erasmus University Rotterdam|
|Note||For copyright reasons there is a (partial) embargo for this dissertation|
Vougioukalaki, M. (2019, February 20). Impact of Endogenous Genomic Damage on Adult Stem Cells and Tissue Homeostasis. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/115132