How might cohesin hold sister chromatids together?

Abstract

The sister chromatid cohesion essential for the bi-orientation of chromosomes on mitotic spindles depends on a multi-subunit complex called cohesin. This paper reviews the evidence that cohesin is directly responsible for holding sister DNAs together and considers how it might perform this function in the light of recent data on its structure.

Figure 1

Models for sister chromatid cohesion according to which SMC ATPase heads bind DNA.

Figure 2

Scc1 inter-connects two Smc1/Smc3 heterodimers that bridge sister DNAs.

Figure 3

Might interactions between SMC hinges or between SMC coiled coils mediate the connection between sister DNAs?

Figure 4

Cohesin forms a ring structure that might entrap DNA.

Figure 5

Crystal structure of a dimeric hinge domain from Thermatoga maritima (Haering et al. 2002).

Figure 6

Crystal structure of a dimeric Smc1 ATPase head complexed with Scc1's C-terminal winged helix (Haering et al. 2004).

Figure 7

ATP binding might bring Smc1 and Smc3 heads together while its hydrolysis would drive them apart.

Figure 8

Evidence that Scc1's N-terminal domain binds to cohesin's Smc3 head. Separase activity in vivo cleaves Scc1 and releases cohesin from chromosomes, while severing Smc3's coiled coils in vitro releases the Smc3 head and Scc1's N-terminal cleavage fragment from the rest of cohesin.

Figure 9

Models in which Scc1 links Smc1 and Smc3 ATPase heads from different Smc1/Smc3 heterodimers, either forming a dimeric ring (a) or a filament (b).

Figure 10

Transcription might drive cohesin to regions of convergent transcription and thereby hold sister chromatids in register.

Figure 11

Potential mechanisms by which DNA might be trapped by cohesin rings.