  Eukaryotic DNA replication follows a specific temporal program, with some
genomic regions consistently replicating earlier than others, yet what
determines this program is largely unknown. Highly transcribed regions have
been observed to replicate in early S-phase in all plant and animal species
studied to date, but this relationship is thought to be absent from both
budding yeast and fission yeast. No association between cell-cycle regulated
transcription and replication timing has been reported for any species. Here I
show that in budding yeast, fission yeast, and human, the genes most highly
transcribed during S-phase replicate early, whereas those repressed in S-phase
replicate late. Transcription during other cell-cycle phases shows either the
opposite correlation with replication timing, or no relation. The relationship
is strongest near late-firing origins of replication, which is not consistent
with a previously proposed model -- that replication timing may affect
transcription -- and instead suggests a potential mechanism involving the
recruitment of limiting replication initiation factors during S-phase. These
results suggest that S-phase transcription may be an important determinant of
DNA replication timing across eukaryotes, which may explain the
well-established association between transcription and replication timing.
