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J. Biol. Chem., Vol. 282, Issue 7, 4447-4452, February 16, 2007

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Perturbation of the Activity of Replication Origin by Meiosis-specific Transcription^*

Saori Mori and Katsuhiko Shirahige¹

From the Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Kanagawa 230-0045, Japan and 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

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.

Received for publication, October 13, 2006 , and in revised form, December 12, 2006.

^* This work was supported by a grant-in-aid for scientific research on priority areas from the Ministry of Education, Science, Sports, and Culture of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-45-924-5812; Fax: 81-45-924-5814; E-mail: kshirahi{at}bio.titech.ac.jp.

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