High impact information on YKU80

• The only protein found to be involved in the peripheral localization of telomeres is Yku70/Yku80 [1].
• Separation of silencing from perinuclear anchoring functions in yeast Ku80, Sir4 and Esc1 proteins [2].
• Here, we show that homologous integration in the filamentous fungus Neurospora requires the homologous-recombination proteins MEI-3 (yeast Rad51 homolog) and MUS-25 (yeast Rad54 homolog), whereas nonhomologous integration requires nonhomologous end-joining protein MUS-52 (yeast Ku80 homolog) [3].
• These results indicate a novel function of yeast Ku80p in regulating mating type switching [4].
• Toward defining these functional differences, we have identified eight mutations in the large subunit of the Saccharomyces cerevisiae Ku heterodimer (YKU80) which retain the ability to repair double-strand breaks but are severely impaired for chromosome end protection [5].

Biological context of YKU80

• Here, we describe the identification of separation-of-function mutants of Yku80p that exhibit defects in silencing but not DNA repair and show that these mutations map to an evolutionarily conserved domain within Yku80p [6].
• We show that overexpression of EST2 or TLC1 in yku80 mutants does not restore efficient DNA repair, or restore normal telomere function, as measured by telomere length, single-stranded G-rich strand or transcriptional silencing [7].
• Instead, yku80 mutants activate a Rad53p-dependent DNA-damage checkpoint at 37 degrees C and this is suppressed by overexpression of EST2 or TLC1 [7].
• Indeed, through using an in vivo plasmid rejoining assay, we find that YKU80 plays an essential role in illegitimate recombination events that result in the accurate repair of restriction enzyme generated DSBs [8].
• Targeted disruption of the HDF2 gene causes a temperature-sensitive phenotype for growth comparable to the phenotype of hdf1(-) strains [9].

Associations of YKU80 with chemical compounds

• The human Ku protein cannot complement this temperature-sensitive phenotype. hdf2(-) strains are sensitive to bleomycin and methyl methanesulfonate, but this sensitivity is reduced in comparison with hdf1(-) strains [9].

Physical interactions of YKU80

• Furthermore, we reveal that Yku80p interacts with the silent information regulator protein Sir4p and that this interaction is mediated by the N-terminal 200 amino acid residues of Sir4p [6].

Regulatory relationships of YKU80

• Indeed, deletion of genes required for Rad53p activation also suppresses the yku80 temperature sensitivity [7].
• Significantly, we find that YKU80 disruption enhances the radiosensitivity of rad52 mutant strains, suggesting that YKU80 functions in a DNA DSB repair pathway that does not rely on homologous recombination [8].

Other interactions of YKU80

• We report that deletion of YKU70 or YKU80 suppresses mec1Delta, but not rad53Delta, lethality [10].
• A rare RAD52- and YKU80-independent form of deletion was present in all strains [11].
• Epistasis analysis also indicated that YKU80 and RAD9/RAD24 function in the same pathway for repair of lesions caused by MMS and gamma-irradiation [12].

References