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Regulating nuclear organisation in telomere maintenance and DNA repair: the role of SUMO modification

Final Report Summary - SUMO AND CHROMATIN (Regulating nuclear organisation in telomere maintenance and DNA repair: the role of SUMO modification)

The genetic information of all cells is contained within the sequence of DNA that makes up its genome. Importantly however, DNA is not naked within the nucleus but is complexed with histone proteins to form chromatin. It has been shown that chromatin structure can be modulated to regulate access to the underlying DNA. Thus, chromatin is a key means of regulating where and when DNA can be accessed and is therefore important for all aspects of DNA metabolism. Recently, growing evidence has suggested that not only is chromatin structure important but also chromatin localisation, i.e. where within the nucleus it is found.

Telomeres contain a specialised chromatin structure that consist of TG rich DNA sequence repeats and associated binding proteins that form the ends of all linear chromosomes. These serve to protect chromosome ends from being recognised as double strand breaks (DSBs) which would otherwise result in either cell cycle arrest or eventual genome instability. In budding yeast, telomeres show a particularly distinctive nuclear localisation; being reversibly bound to the nuclear periphery. The organisation of chromatin into spatially and functionally distinct compartments is thought to promote the efficient completion of fundamental nuclear processes such as transcription and DNA repair. This is perhaps especially important for telomeres, where it has been shown that altered nuclear localisation and dynamics can result in an inappropriate repair response.

Telomere anchoring in S. cerevisiae occurs via two partially redundant genetic pathways acting via either Sir4 or the Yku70/80 heterodimer. Interestingly, the relative influence of these pathways changes throughout the cell cycle and also from telomere