In yeast, HDF1 and HDF2 encode Ku70p and Ku80p and, together with other genes including DNL4, XRS2, MRE11, and RAD50, are required for NHEJ ( Boulton and Jackson 1996a, b Moore and Haber 1996 Teo and Jackson 1997). In mammalian cells, DNA protein kinase and KU70/85 carry out NHEJ, which can occur in response to double strand breaks. 1993).Ī growing body of evidence suggests that the Sir proteins are also involved in nonhomologous end joining (NHEJ), which is used to repair breaks in DNA by ligation of the free ends (for review, see Critchlow and Jackson 1998). Sir3p and Sir4p can be visualized at telomeric locations microscopically, and sir mutations result in a loss of PEV, telomere shortening, and the constitutive expression of telomeric reporter genes ( Aparicio et al. An additional function of SIR2, SIR3, and SIR4 was demonstrated by showing that reporter genes positioned at telomere-proximal sequences exhibit positional effect variegation (PEV) of gene expression ( Gottschling et al. Loss of silencing at these loci results in coexpression of a and α mating type genes and sterility in haploid strains. SIR1, SIR2, SIR3, and SIR4 were first identified as necessary components for the transcriptional repression of the silent mating type loci, HML and HMR ( Ivy et al. In the budding yeast Saccharomyces cerevisiae, the SIR ( silent information regulator) genes serve several functions.
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