Functions of Rad16 Endonuclease at Telomeres in S. pombe

Abstract

Telomeres are nucleoprotein structures that protect the ends of linear chromosomes from degradation and end-to-end fusions mediated by DNA-damage response proteins. Interestingly, accumulating evidence in recent years indicates that multiple proteins involved in DNA damage response pathways are localized to telomeres and actively participate in regulating telomeres. The ERCC1/XPF heterodimer is a highly conserved endonuclease complex which functions in multiple DNA repair pathways. Deficiencies in human ERCC1/XPF result in Xeroderma Pigmentosum (XP), a disease that is characterized by sensitivity to UV light and a high incidence of skin tumors. Our work shows that fission yeast rad16+, the homolog to mammalian XPF, is synthetic lethal with pot1+, the gene encoding the protection of telomeres protein which binds to single-stranded telomere DNA. Further study indicates that a portion of Rad16 is physically associated with telomeres and plays various roles when the protecting structure of telomeres is disrupted. Upon loss of telomeres in the pot1+ or telomerase null cells, survivor strains emerge through intra-chromosome fusions of all three chromosomes. Lack of Rad16 blocks the survival mechanisms in the pot1+ or telomerase null cells but does not affect taz1+ null cells. Our data suggests roles for Rad16 in chromosome circularization and in the maintenance of circular chromosomes during mitotic growth.