High impact information on CTF4

• Consistent with this interpretation, one of the binding proteins, which we have named POB1 (polymerase one binding), is required for normal chromosome transmission [1].
• The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion [2].
• Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion [2].
• A complex of GINS and Ctf4 has an important function in coupling MCM2-7 helicase to DNA polymerase α in budding yeast [3]
• CDC68 also interacted genetically with POL1 and CTF4 mutations; the maximum permissive temperature of double mutants was lower than for any single mutant [4].
• The binding of both proteins was enhanced when extracts lacking a previously characterized polymerase binding protein, Ctf4, were used [4].

Biological context of CTF4

• The sequence of the POB1 gene indicates that it is identical to the CTF4 (CHL15) gene identified previously in screens for mutations that diminish the fidelity of chromosome transmission [5].
• Our finding that cells deleted for CTF8, CTF4 or CHL1 undergo massive meiosis II non-disjunction suggests that the second meiotic division is particularly sensitive to cohesion defects [6].
• Using a functional as well as a cytological assay, we demonstrate that CTF8, CHL1 and CTF4 are essential for cohesion between sister centromeres during meiosis but dispensable for cohesin's association with centromeric DNA [6].
• Analysis of sequences upstream of the CTF4 open reading frame revealed the presence of a hexamer element, ACGCGT, a sequence associated with many DNA metabolism genes in budding yeasts [7].
• Disruption of the coding sequence of CTF4 did not result in inviability, indicating that the CTF4 gene is nonessential for mitotic cell division [7].

Anatomical context of CTF4

• We speculate that Pob1p is located on growing plasma membrane, possibly through the function of actin patches, and may recruit proteins required for the synthesis of cell wall [8].

Associations of CTF4 with chemical compounds

• Both inter- and intrachromosomal mitotic recombination levels are elevated in ctf4 mutants, whereas spontaneous mutation to canavanine resistance was not elevated [7].
• Evidence that POB1, a Saccharomyces cerevisiae protein that binds to DNA polymerase alpha, acts in DNA metabolism in vivo [5].

Other interactions of CTF4

• Full activity of the Dna2 helicase function is therefore not needed for viability, but is required for repairing damage and for tolerating loss of Ctf4 [9].
• The ability of Ctf4 to couple DNA polymerase α to MCM helicase through the GINS complex is particularly crucial in cells that lack Mrc1 [3]
• Based on tetrad analysis, chl12, chl14 and chl15 correspond to mutations in single nuclear genes [10].
• The CHL15 gene is tightly linked to the KAR3 marker of the right arm of chromosome XVI (8.8 cM) [10].
• Dna2 therefore appears to act in repair or lagging strand synthesis together with Pol alpha and Ctf4, in a role that is optimal with, but does not require, full helicase activity [9].
• We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint [2].

Analytical, diagnostic and therapeutic context of CTF4

• Analysis using the pob1-ts allele revealed that Pob1p is also essential for cell separation [8].

References