New & Noteworthy

Cln2p Moonlights in Cohesion

July 22, 2022

In an interesting new development, two different teams using two different sets of genetic interactions came to the same conclusion that Cln2p has a role in sister chromatid cohesion separate from its well-known role as a cyclin.

In a recent issue of the journal G3 (Bethesda), Buskirk and Skibbens report how deletion of the G1 cyclin CLN2 can rescue the temperature-sensitive growth defects of a strain lacking both ECO1 and RAD61, which are involved in regulation of sister chromatid cohesion. The authors show that neither CLN1 nor CLN3 deletion has the same effect, so the function is unique to CLN2. This result is especially interesting considering that CLN1 and CLN2 are paralogs resulting from whole genome duplication.

The authors show by genetic interaction how the role of Cln2p in sister chromatid cohesion is independent of its role in the G1/S cell cycle transition. Given that Cln2p activates Cdc28p within the CLN2-CDC28 kinase complex (Cln2-CDK) to trigger post-Start processes, the authors asked whether the whole complex has a role in cohesion. By looking closely at phenotypes of condensation, they conclude that this particular cyclin kinase complex plays a role in DNA hypercondensation, but that other CDKs interact with Eco1p at other points in the cell cycle.

Using a similar but different approach, Choudhary et al. in a recent issue of mBio likewise looked for suppressors of a chromatid cohesion defect causing temperature-sensitive growth. In this case, they use a double mutant lacking Pds5p, a protein associated with the cohesin complex, and Elg1p, a protein involved in DNA replication. The elg1Δ mutation can suppress the pds5-1 temperature-sensitive allele but not the full deletion, such that the double mutant is inviable.

In a screen for mutants that rescued this lethality, 23 of 40 isolates carried mutations in the CLN2 gene. Deletion of the paralog CLN1 could not rescue the lethality of the pds5Δ elg1Δ double mutant, again suggesting these paralogs are not functionally redundant. Further investigation showed how cln2Δ deletion caused overexpression of MCD1, encoding the alpha-kleisin subunit of the cohesin complex. MCD1 has two promoter elements bound by the MBF transcription complex, and removal of these elements abrogated the overexpression. Thus, consistent with previous studies, the absence of CLN2 somehow caused overexpression of genes regulated by the MBF complex, in this case a critical cohesin subunit.

We expect to hear more about the role of Cln2p in cohesion, for this secondary role is intriguing. It may be the case that other MBF-regulated genes are overexpressed when CLN2 is absent, and this might give rise to other roles. Given the complexity of these multifunction proteins, the yeast model provides a strong platform for answering the next questions.

Categories: Research Spotlight

Tags: cell cycle regulation , checkpoint proteins , mitotic cell cycle , Saccharomyces cerevisiae , sister chromatid cohesion