Abstract
We have determined the activity of all ARSs on the Saccharomyces cerevisiae chromosome VI as chromosomal replication origins in premeiotic S-phase by neutral/neutral two-dimensional gel electrophoresis. The comparison of origin activity of each origin in mitotic and premeiotic S-phase showed that one of the most efficient origins in mitotic S-phase, ARS605, was completely inhibited in premeiotic S-phase. ARS605 is located within the open reading frame of MSH4 gene that is transcribed specifically during an early stage of meiosis. Systematic analysis of relationships between MSH4 transcription and ARS605 origin activity revealed that transcription of MSH4 inhibited the ARS605 origin activity by removing origin recognition complex from ARS605. Deletion of UME6, a transcription factor responsible for repressing MSH4 during mitotic S-phase, resulted in inactivation of ARS605 in mitosis. Our finding is the first demonstration that the transcriptional regulation on the replication origin activity is related to changes in cell physiology. These results may provide insights into changes in replication origin activity in embryonic cell cycle during early developmental stages.
Highlights
Eukaryotic chromosomes consist of multiple replication units
Transcription of MSH4 Interferes with Origin Activity of ARS605 in Meiosis—To confirm our hypothesis, we examined the relationships between MSH4 transcription and
We have demonstrated that Orc1 binding to ARS605 origin was reduced in parallel with the increase in MSH4 transcription
Summary
Eukaryotic chromosomes consist of multiple replication units. Each origin of DNA replication is strictly controlled to fire only once in the cell cycle in the fixed sequential order [1, 2]. Recent genome-wide studies of eukaryotic chromosomal DNA replication using Saccharomyces cerevisiae have provided us with a kinetic map of progression of DNA replication along the chromosome [5, 6] These studies were restricted to DNA replication during mitotic cell cycle and little is known about how these multiple replication origins behave under different cell cycle, i.e. meiotic cell cycle. Cha et al [14] showed that Spo, which is required for interhomolog interaction, and Rec, a meiosisspecific cohesin subunit, are negative and positive regulators for the progression of premeiotic S-phase, respectively These results suggest that there are many other possible regulations of replication at each chromosomal level that affect the progression of S-phase in meiotic cell cycle
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
