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

CTF7 (chromosome transmission fidelity) gene in budding yeast encodes an es sential protein that is required for high-fidelity chromosome transmission and contains regions of identity conserved from yeast to man, ctf7 mutant c ells arrested prior to anaphase onset contain separated sister chromatids. Thus, Ctf7p is essential for cohesion. Cohesion is established during S pha se and then maintained until mitosis. However, Ctf7p activity is required o nly during S phase, suggesting that Ctf7p functions in the establishment of cohesion. In addition, ctf7 genetically interacts with DNA metabolism muta tions po130 (PCNA) and ctf18 tan RE-C like protein) and ctf7 temperature se nsitivity and chromosome loss are rescued by high levels of POL30. These fi ndings provide the first evidence that links the establishment of sister ch romatid cohesion to the DNA replication machinery and suggest that the asse mbly of cohesion land 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 spi ndle assemby checkpoint.