Chromatin silencing depends on passage through the S-phase of the cell cycle and was widely believed to depend on DNA replication. In two papers in the January 26 Science, Kirchmaier and Rine and Li et al. challenge this dogma by reporting that the establishment of transcriptional silencing can occur in the absence of replication (Science 2001, 291:646-650; Science 2001, 291:650-653). Both groups used an ingenious genetic trick, involving site-specific recombination, to generate non-replicating DNA rings containing the silent HMR mating-type locus from budding yeast. Recruiting the silencing protein Sir1 induced silencing at the synthetic silencer without any detectable DNA replication. Furthermore, the authors show that the artificial silent rings mimic features of authentic heterochromatin, including histone hypoacetylation and altered supercoiling. Strangely, despite being independent of replication, silencing still required passage through the S-phase of the cell cycle.

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