Regulation of telomere maintenance and protection in fission yeast.

摘要

The appropriate maintenance of telomeres is crucial to prevent end fusions, recombination and loss of genetic material. Therefore, the study of the regulation of telomere maintenance and protection in the context of heterochromatin proteins, telomere-associated proteins as well as checkpoint proteins was investigated.;The regulation of telomere recombination has been shown to depend on a multitude of proteins, such as the double-stranded telomeric binding protein Taz1 and the enzyme telomerase, Trt1. In this study we analyzed the genetic requirements of this regulation by deleting the heterochromatin proteins Swi6 and Clr4, as well as the telomere capping complex subunits Ccg1 and Poz1. We were able to show that Taz1 as well as the catalytically inactive form of Trt1 did not require any of these factors to inhibit recombination-based telomere maintenance. On the other hand, our analysis unveiled a role for Swi6, Clr4, Ccg1, the checkpoint kinase Rad3 and the telomerase regulatory subunit Est1 in the enhancement of the ability of a truncated form of telomerase to inhibit telomere recombination.;While telomeres should not be considered to be double-strand breaks, they have been shown to be bound by various checkpoint proteins which play a role in their maintenance. The identification of a hypomorphic allele of one of these checkpoint proteins, DBDrad3, has enabled us to uncover the important role played by the clamp-like 911 complex and the clamp loader RFC complexes in the absence of tel1. Such a genetic background will be useful to identify mutations in these checkpoint proteins that may play a role in telomere maintenance and regulation.