Role of heterochromatin in suppressing subtelomeric recombination in fission yeast

Abstract

Telomere length is regulated by a complex interplay of several factors, including telomerase, telomere-binding proteins, DNA replication machinery and recombination. In yeast, DNA polymerase α is required for de novo synthesis of telomeres from broken ends of DNA, and it also suppresses the elongation of normal telomeric repeats. Heterochromatin proteins Clr1-Clr4 and Swi6 and DNA polα organize heterochromatin structure at mating type, centromere, rDNA and telomere regions that are refractory to transcription and recombination in Schizosaccharomyces pombe. Here, we have addressed the role of heterochromatin structure in regulating the integrity and organization of telomeric regions. Here, we show that subtelomeric duplication and rearrangements occur in polα and heterochromatin mutants and find that some of the putative duplication events are dependent on the Rad50 pathway. Thus, our study shows a role of heterochromatin in maintaining the integrity of the subtelomeric regions by suppressing their recombination in Sz. pombe.

Telomere components as potential therapeutic targets for treating microbial pathogen infections

“…At least two Shelterin homologs have been identified in T. brucei (Li et al, 2005; Yang et al, 2009), which enabled further investigation of the telomere structure in VSG switching regulation. It is speculated that disruption of the heterochromatic telomere structure, especially in the case of depletion of TbRAP1 (Yang et al, 2009), may also lead to higher VSG switching rate, similar to what was observed in S. pombe (Bisht et al, 2008). …”

“…An epigenetic event only affects a gene expression level but does not change its DNA sequences. However, recent studies suggest that epigenetic changes such as chromatin remodeling may also influence genetic events such as DNA recombination (Benetti et al, 2007; Bisht et al, 2008). Common mechanisms of antigenic variation have evolved in different pathogens, including bacteria, fungi, and parasites, possibly due to similar selection pressure exerted from the mammalian immune responses.…”

Telomere as an Important Player in Regulation of Microbial Pathogen Virulence

“…It is possible that disruption of the heterochromatic telomere structure, especially in the case of depletion of TbRAP1, elevated subtelomeric homologous recombination and led to higher VSG switching rate, similar to what was observed in S. pombe (Bisht et al 2008). …”

“…In S. cerevisiae, although subtelomeres are poor substrates for meiotic recombination because chiasmata formed near the ends of chromosomes are much less efficient at promoting homologous chromosome segregation (Su et al 2000), a high level of nucleotide divergence among Saccharomyces yeasts has been observed at the subtelomeres (Teytelman et al 2008). In S. pombe, mutations disrupting heterochromatin led to elevated subtelomeric duplication and rearrangements that are RAD50-dependent, indicating that subtelomeres are susceptible to high rate of homologous recombination but the heterochromatic telomere structure can help suppress these events (Bisht et al 2008). …”

“…An epigenetic event only affects a gene expression level but does not change its DNA sequences. However, recent studies suggest that epigenetic changes such as chromatin remodeling may also influence genetic events such as DNA recombination (Benetti et al 2007;Bisht et al 2008). …”