https://mc06.manuscriptcentral.com/bcb-pubs Biochemistry and Cell Biology D r a f t 1 A decade of understanding spatio-temporal regulation of DNA repair by the nuclear architecture https://mc06.manuscriptcentral.com/bcb-pubs Biochemistry and Cell Biology D r a f t 2 Abstract The nucleus is a hub for gene expression and is a highly organized entity. The nucleoplasm is heterogeneous due to the preferential localization of specific metabolic factors, which led to the definition of nuclear

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... nts or bodies. The genome is organized into chromosome territories, heterochromatin and euchromatin domains. Recent observations indicate that nuclear organization is important for maintaining genomic stability. For example, nuclear organization has been implicated in stabilizing damaged DNA, repair pathway choice and in preventing chromosomal rearrangements. Over the past decade, several studies have revealed that dynamic changes in the nuclear architecture are important during double-strand break repair. Stemming from work in yeast, relocation of a damaged site prior to repair appears to be at least partially conserved in multicellular eukaryotes. In this review, we will discuss genome and nucleoplasm architecture, particularly the importance of the nuclear periphery in genome stability. We will also discuss how the site of relocation regulates repair pathway choice. Page 2 of 34 https://mc06.manuscriptcentral.com/bcb-pubs Biochemistry and Cell Biology