title: Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing.
abstract: In the budding yeast, Saccharomyces cerevisiae, genes in close proximity to telomeres are subject to transcriptional silencing through the process of telomere position effect (TPE). Here, we show that the protein Ku, previously implicated in DNA double-strand break (DSB) repair and in telomeric length maintenance, is also essential for telomeric silencing. Furthermore, using an in vivo plasmid rejoining assay, we demonstrate that SIR2, SIR3 and SIR4, three genes shown previously to function in TPE, are essential for Ku-dependent DSB repair. As is the case for Ku-deficient strains, residual repair operating in the absence of the SIR gene products ensues through an error-prone DNA repair pathway that results in terminal deletions. To identify novel components of the Ku-associated DSB repair pathway, we have tested several other candidate genes for their involvement in DNA DSB repair, telomeric maintenance and TPE. We show that TEL1, a gene required for telomeric length maintenance, is not required for either DNA DSB repair or TPE. However, RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance, although they have no major effects on TPE. These data provide important insights into DNA DSB repair and the linkage of this process to telomere length homeostasis and transcriptional silencing.
authors.affiliation: Wellcome/CRC Institute, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Boulton
authors.forename: S P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: D034961:Antigens, Nuclear; D004265:DNA Helicases; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D005800:Genes, Fungal / Q000502:physiology; D005819:Genetic Markers; D006655:Histone Deacetylases; D000072200:Ku Autoantigen; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D016615:Telomere / Q000235:genetics*; D013696:Temperature; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; C086930:RAD50 protein, S cerevisiae; C084121:SIR1 protein, S cerevisiae; C084122:SIR3 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; C086929:XRS2 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen