Perturbation of the activity of replication origin by meiosis-specific transcription.
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.
Mori
Saori
S
Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Kanagawa 230-0045, Japan and.
Shirahige
Katsuhiko
K
Laboratory of Genome Structure and Function, Division for Gene Research, Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama City, Kanagawa 226-8501, Japan. Electronic address: kshirahi@bio.titech.ac.jp.
D018797:Cell Cycle Proteins / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D004271:DNA, Fungal / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics; D008540:Meiosis / Q000502:physiology*; D016366:Open Reading Frames / Q000235:genetics; D018741:Replication Origin / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D016196:S Phase / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C502328:Msh4 protein, mouse; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C089979:UME6 protein, S cerevisiae