Cell Biology

Perfect Timing

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Science  31 Jul 2009:
Vol. 325, Issue 5940, pp. 519
DOI: 10.1126/science.325_519b

For cell division to occur, DNA must be completely replicated during the S phase of the cell cycle. Replication is tightly controlled, and the timing of replication of different regions of the genome is linked to localization in the nucleus and gene expression; replication timing of some genetic loci changes during development.

Using a nuclear microinjection system, Lande-Diner et al. changed the timing and analyzed histone proteins, which package DNA into nucleosomes to form chromatin. Histones undergo extensive post-translational modifications, which correlate with gene activity. Chromatin replicating late in S phase is generally inactive and packaged with deacetylated histones. They found that when the replication timing of a reporter gene was switched from late to early during S phase, it was repackaged with acetylated histones, which are a marker of active chromatin, and that the opposite occurred when replication was switched from early to late. The switch is due to cell cycle regulation of the acetylation state of histones and indicates how alterations in replication timing, such as that occurring during development, affect chromatin organization and gene activity.

Mol. Cell 34, 767 (2009).

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