Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery

Abstract

CTF7 (chromosome transmission fidelity) gene in budding yeast encodes an essential protein that is required for high-fidelity chromosome transmission and contains regions of identity conserved from yeast to man. ctf7 mutant cells arrested prior to anaphase onset contain separated sister chromatids. Thus, Ctf7p is essential for cohesion. Cohesion is established during S phase and then maintained until mitosis. However, Ctf7p activity is required only during S phase, suggesting that Ctf7p functions in the establishment of cohesion. In addition, ctf7 genetically interacts with DNA metabolism mutations pol30 (PCNA) and ctf18 (an RF-C like protein) and ctf7 temperature sensitivity and chromosome loss are rescued by high levels of POL30. These findings provide the first evidence that links the establishment of sister chromatid cohesion to the DNA replication machinery and suggest that the assembly of cohesion (and possibly condensation) complexes are coupled to PCNA-dependent DNA replication. The analysis of Ctf7p also reveals an important connection between sister chromatid cohesion, spindle integrity and the spindle assemby checkpoint.

Characterization of the components of the putative mammalian sister chromatid cohesion complex

“…The PCNA and Ctf7 proteins are conserved between mouse and budding yeast. If a hypothetical PCNA/Ctf7p complex is involved in loading 'chromatid glue' onto DNA after chromatin replication as proposed (Skibbens et al, 1999), one might expect PW29 and PCNA to exhibit similar localization patterns. The fact that they do not fully colocalize in mouse cells may indicate that the PCNA/Ctf7 pathway is independent of the mSMCB-mSMCD-PW29 pathway.…”

“…PCNA has been linked to the recently identified S. cerevisiae cohesion factor Ctf7p, whose mechanistic role in cohesion has not yet been established. A temperature-sensitive mutation in yeast CTF7 is suppressed by the yeast gene for PCNA, POL30 (Skibbens et al, 1999). The PCNA and Ctf7 proteins are conserved between mouse and budding yeast.…”

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

“…Ctf7/Eco1 (Esco2/Efo2, Deco, Eso1) Similar to Pds5, the Ctf7/Eco1 protein of S. cerevisiae and the S. pombe Eso1 ortholog are not required for binding of cohesin to chromosomes, but are needed to establish cohesion during S phase (Skibbens et al 1999;Tanaka et al 2000;Toth et al 1999). Ctf7/Eco1 associates with a replication factor C complex, a PCNA sliding clamp loader, suggesting that it has a critical role during DNA replication .…”

The INO80 Chromatin Remodeling Complex Functions in Sister Chromatid Cohesion

“…Circumstantial evidence has indeed indicated a relationship between DNA replication and the establishment of sister chromatid cohesion. Sister chromatid cohesion requires not only chromosome-bound cohesin complexes but also Eco1 and PCNA, 4,6,28 as well as several accessory factors such as Ctf18. 29,30 These proteins locali�e to replication forks, at least when cells are arrested in early S phase by hydroxy urea (HU) treatment.…”

“…Interaction between PCNA and Eco1 is required for the Eco1 function in sister chromatid cohesion and for its timely recruitment to chromatin. [4][5][6] These cohesion proteins have been locali�ed to replication forks.…”