COMPONENTS OF THE KU-DEPENDENT NONHOMOLOGOUS END-JOINING PATHWAY ARE INVOLVED IN TELOMERIC LENGTH MAINTENANCE AND TELOMERIC SILENCING

In the budding yeast, Saccharomyces cerevisiae, genes in close proximi ty to telomeres are subject to transcriptional silencing through the p rocess of telomere position effect (TPE), Here, we show that the prote in Ku, previously implicated in DNA double-strand break (DSE) repair a nd in telomeric length maintenance, is also essential for telomeric si lencing, Furthermore, using an in vivo plasmid rejoining assay, we dem onstrate that SIR2, SIR3 and SIR4, three genes shown previously to fun ction in TPE, are essential for Ku-dependent DSB repair, As is the cas e for Ku-deficient strains, residual repair operating in the absence o f the SIR gene products ensues through an error-prone DNA repair pathw ay that results in terminal deletions, To identify novel components of the Ku-associated DSB repair pathway, we have tested several other ca ndidate genes for their involvement in DNA DSB repair, telomeric maint enance and TPE, We show that TEL1, a gene required for telomeric lengt h maintenance, is not required for either DNA DSB repair or TPE, Howev er, RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance, although they have no major effe cts on TPE, These data provide important insights into DNA DSB repair and the linkage of this process to telomere length homeostasis and tra nscriptional silencing.