Yeast telomeres exert a position effect on recombination between internal tracts of yeast telomeric DNA

Abstract

In Saccharomyces cerevisiae, proximity to a telomere affects both transcription and replication of adjacent DNA. In this study, we show that telomeres also impose a position effect on mitotic recombination. The rate of recombination between directly repeated tracts of telomeric C 1-3 A/TG 1-3 DNA was reduced severely by proximity to a telomere. In contrast, recombination of two control substrates was not affected by telomere proximity. Thus, unlike position effects on transcription or replication, inhibition of recombination was sequence specific. Moreover, the repression of recombination was not under the same control as transcriptional repression (telomere position effect; TPE), as mutations in genes essential for TPE did not alleviate telomeric repression of recombination. The reduction in recombination between C 1-3 A/TG 1-3 tracts near the telomere was caused by an absence of Rad52p-dependent events as well as a reduction in Rad1p-dependent events. The sequence-specific repression of recombination near the telomere was eliminated in cells that overexpressed the telomere-binding protein Rap1p, a condition that also increased recombination between C 1-3 A/TG 1-3 tracts at internal positions on the chromosome. We propose that the specific inhibition between C 1-3 A/TG 1-3 tracts near the telomere occurs through the action of a telomere-specific end-binding protein that binds to the single-strand TG 1-3 tail generated during the processing of recombination intermediates. The recombination inhibitor protein may also block recombination between endogenous telomeres.[Key Words: Telomeres; recombination; yeast; position effect; telomere replication] Received April 29, 1998; revised version accepted August 3, 1998.In most organisms, telomeres consist of simple repetitive DNA. For example, each end of each Saccharomyces chromosome bears ∼300 bp of C 1-3 A/TG 1-3 DNA. Telomeres are required for the stable maintenance and segregation of yeast chromosomes (Sandell and Zakian 1993). In most organisms, including yeast, telomeric DNA is replicated by telomerase, a telomere-specific reverse transcriptase (for review, see Greider 1995). Telomerase extends the G-strand of telomeric DNA using its RNA component as a template. Telomerase-independent pathways for telomere replication also exist. In yeasts (Lundblad and Blackburn 1993;McEachern and Blackburn 1995;Lendvay et al. 1996) and human cells in culture (Murnane et al. 1994;de Lange 1995;Rogan et al. 1995), telomere-telomere recombination can maintain telomeric DNA in the absence of telomerase. In some insects, recombination is probably the sole pathway for maintenance of telomeric DNA (Biessmann et al. 1996;Lopez et al. 1996).The subtelomeric regions of chromosomes from many organisms, including yeast, consist of a variable array of middle repetitive DNA with the variability caused, at least in part, by homologous recombination among the repeats (Brown et al. 1990;Louis et al. 1994). In yeast, the number and identity of these middle repetitive elements vary, both from stra...

Role of heterochromatin in suppressing subtelomeric recombination in fission yeast

“…pombe. In contrast, sir mutations in budding yeast, which abrogate the position-effect control of transcription at the telomere (Gottschling et al, 1990) and enhance the accessibility of telomeres to dam methylase (Gottschling, 1992), do not abrogate the recombination block at telomeres; rather, it is abrogated by mutations in recombination pathways such as Rad51 (Stavenhagen and Zakian, 1998). Although similar recombination events have not been reported in other organisms, the possibility of heterochromatin playing a role in suppressing recombination in other systems is not ruled out.…”

“…Studies in the budding yeast have shown that heterochromatin regulates the telomere position effect, but surprisingly has no effect on telomere recombination; rather, aberrant recombination was reported in mutants in the Rad50 pathway (Stavenhagen and Zakian, 1998). In human cells, mutations in the histone methyltransferases Suv39h1 and Suv39h2 genes have been found to elicit telomere repeat elongation (Garcia-Cao et al, 2004).…”

InSaccharomyces cerevisiae, yKu and Subtelomeric Core X Sequences Repress Homologous Recombination Near Telomeres as Part of the Same Pathway

“…Allelic recombination was not altered significantly when leu2 heteroalleles were placed at proximal subtelomeric and interstitial loci (Lichten and Haber 1989) and between direct repeats placed at subtelomeric and interstitial loci (Stavenhagen and Zakian 1998). We have proposed a model where a recombination barrier is set up between subtelomeric and interstitial sequences via nuclear tethering based on sequence analysis and preliminary recombination studies .…”

High frequency mitotic gene conversion in genetic hybrids of the oomycete Phytophthora sojae

“…44) or by the addition or removal of methyl groups (as in bacterial-style restriction-modification systems). Alteration of chromatin configuration similar to position effects on transcription (42,45) is a third possibility.…”