PCNA promotes cohesion establishment in a context-dependent manner

2020-04-20T23:12:42Z (GMT) by Caitlin Zuilkoski Robert Skibbens

Cellular genomes undergo various structural changes that include cis tethering (the tethering together of two loci within a single DNA molecule), which occurs during DNA condensation and transcriptional activation, and trans tethering (the tethering together of two DNA molecules), which occurs during cohesion establishment and DNA repair. The protein complex termed cohesin promotes both cis and trans forms of DNA tethering, but these cohesin functions appear to occur in both temporal and context-specific regulated mechanisms. For instance, cohesion establishment occurs in the context of the DNA replication fork in which PCNA recruits Eco1 to convert chromatin-bound cohesins to a tethering competent state. In support for this model, elevated levels of PCNA rescue cell viability and cohesion defects in eco1 mutant cells.

Here, we test whether Eco1-dependent chromatin condensation is also promoted in the context of this replication fork component. Our results reveal that overexpressed PCNA does not promote DNA condensation in eco1 mutant cells, even though levels of Smc3 acetylation are increased. In combination, our data suggests that one cohesin population promotes sister chromatid cohesion in context of the DNA replication fork, whereas an alternate cohesin population participates in chromatin condensation outside the context of the DNA replication fork.