Unzipped and loaded: the role of DNA helicases and RFC clamp-loading complexes in sister chromatid cohesion

Abstract

It is well known that the products of chromosome replication are paired to ensure that the sisters segregate away from each other during mitosis. A key issue is how cells pair sister chromatids but preclude the catastrophic pairing of nonsister chromatids. The identification of both replication factor C and DNA helicases as critical for sister chromatid pairing has brought new insights into this fundamental process.

Figure 1.

Replication through a ring model. DNA replication fork (Pol) passes through a huge cohesin ring (green ring), passively establishing cohesion by entrapping both sisters within a single cohesin ring.

Figure 2.

An active view of cohesion establishment. Sister chromatids become paired via association of separate cohesin rings after DNA replication. This model allows for separation of loci even in the presence of properly deposited cohesins, as observed at centromeres in wild-type cells and throughout chromosomes in ctf7 mutant cells. For convenience, sister pairing is depicted as ring catenation; numerous alternate ring-bridging structures (and contributions by DNA catenation) are equally plausible (Campbell and Cohen-Fix, 2002; Milutinovich and Koshland, 2003).

Figure 3.

A multi-step model of cohesion establishment. (Left) A subset of structural cohesins associated with DNA in G₁ defines precohesion sites. Precohesion sites may be marked by cohesins that remain from the previous cell cycle or by Scc2p–Scc4p-dependent deposition. (Middle) DNA helicases (purple hexameric ring) modify precohesion complexes (broken yellow rings) or promote new cohesin deposition onto single-stranded DNA. (Right) After replication (DNA polymerase), Ct7p-RFC-PCNA (red/pink triangle–ball complex with blue PCNA disc) is posited to pair cohesin rings together, establishing cohesion between sister chromatids (ring catenation shown for simplicity). Black lines represent DNA strands; dashed lines represent RNA primers (primase not depicted) used for Okazaki fragment synthesis during lagging strand synthesis.