DNA double-strand breaks trigger genome-wide sister-chromatid cohesion through Eco1 (Ctf7).
Faithful chromosome segregation and repair of DNA double-strand breaks (DSBs) require cohesin, the protein complex that mediates sister-chromatid cohesion. Cohesion between sister chromatids is thought to be generated only during ongoing DNA replication by an obligate coupling between cohesion establishment factors such as Eco1 (Ctf7) and the replisome. Using budding yeast, we challenge this model by showing that cohesion is generated by an Eco1-dependent but replication-independent mechanism in response to DSBs in G(2)/M. Furthermore, our studies reveal that Eco1 has two functions: a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. Finally, the DSB-induced cohesion is not limited to broken chromosomes but occurs also on unbroken chromosomes, suggesting that the DNA damage checkpoint through Eco1 provides genome-wide protection of chromosome integrity.
Unal
Elçin
E
Carnegie Institution, Howard Hughes Medical Institute, Department of Embryology, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Heidinger-Pauli
Jill M
JM
Koshland
Douglas
D
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002842:Chromatids / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000502:physiology; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis / Q000378:metabolism; D016195:G2 Phase; D016681:Genome, Fungal; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C118076:ECO1 protein, S cerevisiae