Shelterin Mediates Genome Reorganization in Response to Replication Stress (Microarray CGH)

The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability, and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, high-resolution Hi-C analysis revealed prominent new interactions between telomeres and chromosomal arm regions containing replication origins proximal to binding sites for Taz1, a component of the Shelterin telomere protection complex. Strikingly, we find that Shelterin components promote interactions between Taz1-associated chromosomal arm regions and telomeres. These analyses reveal an unexpected role for Shelterin in genome reorganization in cells experiencing replication stress, which has important implications for understanding mechanisms governing replication and genome stability. Microarray CGH analysis in fission yeast cell. Copy number analysis: WT vs. sap1-1 revertant.