Heterochromatin is late

Heterochromatin is late n 1953—the year that Watson and Crick published those findings " of considerable biological interest " —Howard and Pelc (1953) showed that DNA synthesis occurred in a discrete phase of the cell cycle. They had labeled DNA with radioactive phosphate. But better spatial localization of replication required a lower energy and thus more highly localized radioactive probe. This was tritiated thymidine, which Taylor et al. (1957) used to show that DNA replication was restricted to one sister chromatid and thus semi-conservative. The biochemical proof of the same principle came only in the following year, from Meselson and Stahl (1958). Into this flurry of activity came Lima-de-Faria (1959), who showed that heterochromatin replicated later than euchromatin. Heterochromatin was first identified as a darkly staining, condensed material whose significance was unclear. Lima-de-Faria injected tritium-labeled thymidine into grasshopper abdomens and then looked at developing spermatocytes. As the spermatocytes developed in a clear geographical sequence, replication events occurring at different times could be ordered. " The evidence, " wrote Lima-de-Faria, " [was] clear. The tritium was incorporated into heterochromatin later than into euchromatin. " Heterochromatin in rye leaves also replicated at a different time, and late replication of heterochromatin was confirmed in detail by Taylor (1960). The biological importance of this finding " is an important issue, " says Danesh Moazed (Harvard Medical School, Boston, I MA). " But over the years nothing has come of it. " The late replication may help set up the heterochro-matic state, but equally " it may be a side effect of the DNA being less accessible, " says Moazed. Miller and Nasmyth (1984) showed that passage through S phase was required for heterochro-matin to be established in budding yeast. But Kirchmaier and Rine (2001) and Li and Gartenberg Only heterochromatin is labeled in this spermatocyte. (2001) , while confirming the need for an S-phase event, found that DNA replication was not required. Whatever the outcome, Lima-de-Faria's initial result remains unassailable. It also led others to consider DNA replication not as a simple, monolithic process, but as something that was complex and potentially regulated. The nucleolar origin of rRNA he nucleolus was identified early on as a site that made a lot of RNA (Caspersson and Schultz, 1940); later that RNA was shown to have metabolic dynamics distinct from those of chromosomally-derived RNA (McMaster-Kaye and Taylor, 1958). But the function of RNA made in the …