The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Sus1 is a conserved protein essential for histone H2B de-ubiquitination and mRNA export.
• Sus1 partners are implicated in genome integrity, including telomere homeostasis.
• The specific role of Sus1 in telomere maintenance was previously unknown.

Purpose of the Study:

• To investigate the role of Sus1 in telomere maintenance.
• To determine the relationship between Sus1, histone modification, and telomere length.
• To explore Sus1's interaction with telomere maintenance factors.

Main Methods:

• Yeast genetics: analyzing deletion mutants (sus1Δ, sem1Δ, esc2Δ, rsc2Δ) and double mutants.
• Biochemical assays: assessing physical and genetic interactions between Sus1 and telomere factors.
• Histone modification analysis: quantifying mono-ubiquitinated histone H2B levels (H2BK123ub¹).

Main Results:

• Yeast Sus1 physically and genetically interacts with telomere maintenance factors.
• Sus1 absence (sus1Δ) results in elongated telomeres, even in telomere-shortening mutant backgrounds (sem1Δ, esc2Δ, rsc2Δ).
• Sus1 modulates H2BK123ub¹ levels, with sus1Δ mutants showing higher levels and longer telomeres compared to rsc2Δ mutants.

Conclusions:

• Sus1 negatively regulates telomere length.
• This regulation is linked to Sus1's function in histone H2B de-ubiquitination (H2BK123ub¹ modulation).
• Sus1's role in telomere length control involves interactions with the nuclear pore complex.