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DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7)
Elçin Ünal,1,2Jill M. Heidinger-Pauli,1,2Douglas Koshland1*
Faithful chromosome segregation and repair of DNA double-strandbreaks (DSBs) require cohesin, the protein complex that mediatessister-chromatid cohesion. Cohesion between sister chromatidsis thought to be generated only during ongoing DNA replicationby an obligate coupling between cohesion establishment factorssuch as Eco1 (Ctf7) and the replisome. Using budding yeast,we challenge this model by showing that cohesion is generatedby an Eco1-dependent but replication-independent mechanism inresponse to DSBs in G2/M. Furthermore, our studies reveal thatEco1 has two functions: a cohesive activity and a conservedacetyltransferase activity, which triggers the generation ofcohesion in response to the DSB and the DNA damage checkpoint.Finally, the DSB-induced cohesion is not limited to broken chromosomesbut occurs also on unbroken chromosomes, suggesting that theDNA damage checkpoint through Eco1 provides genome-wide protectionof chromosome integrity.
1 Carnegie Institution, Howard Hughes Medical Institute, Department of Embryology, 3520 San Martin Drive, Baltimore, MD 21218, USA. 2 Johns Hopkins University, Department of Biology, 3400 North Charles Street, Baltimore, MD 21218, USA.
* To whom correspondence should be addressed. E-mail: koshland{at}ciwemb.edu
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