Regulation of DNA-replication origins during cell-cycle progression

Katsuhiko Shirahige, Yuji Hori, Katsuya Shiraishi, Minoru Yamashita, Keiko Takahashi, Chikashi Obuse, Toshiki Tsurimoto, Hiroshi Yoshikawa

Research output: Contribution to journalArticle

343 Citations (Scopus)

Abstract

We have shown previously that chromosome VI of Saccharomyces cerevisiae contains nine origins of DNA replication that differ in initiation frequency and replicate sequentially during the S phase of the cell cycle. Here we show that there are links between activation of these multiple origins and regulation of S-phase progression. We study the effects of a DNA-damaging agent, methyl methane sulphonate (MMS), and of mutations in checkpoint genes such as rad53 (ref. 3) on the activity of origins, measured by two- dimensional gel analysis, and on cell-cycle progression, measured by fluorescence-activated cell sorting. We find that when MMS slows down S- phase progression it also selectively blocks initiation from late origins. A rad53 mutation enhances late and/or inefficient origins and releases the initiation block by MMS. Mutation of rad53 also results in a late origin becoming early replicating. We conclude that rad53 regulates the timing of initiation of replication from late origins during normal cell growth and blocks initiation from late origins in MMS-treated cells. tad53 is, therefore, involved in the cell's surveillance of S-phase progression. We also find that orc2, which encodes sub-unit 2 of the origin-recognition complex is involved in suppression of late origins.

Original languageEnglish
Pages (from-to)618-621
Number of pages4
JournalNature
Volume395
Issue number6702
DOIs
Publication statusPublished - Oct 8 1998
Externally publishedYes

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Replication Origin
Methane
DNA Replication
S Phase
Cell Cycle
Mutation
Origin Recognition Complex
Saccharomyces cerevisiae
Flow Cytometry
Chromosomes
Gels
DNA
Growth
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Shirahige, K., Hori, Y., Shiraishi, K., Yamashita, M., Takahashi, K., Obuse, C., ... Yoshikawa, H. (1998). Regulation of DNA-replication origins during cell-cycle progression. Nature, 395(6702), 618-621. https://doi.org/10.1038/27007

Regulation of DNA-replication origins during cell-cycle progression. / Shirahige, Katsuhiko; Hori, Yuji; Shiraishi, Katsuya; Yamashita, Minoru; Takahashi, Keiko; Obuse, Chikashi; Tsurimoto, Toshiki; Yoshikawa, Hiroshi.

In: Nature, Vol. 395, No. 6702, 08.10.1998, p. 618-621.

Research output: Contribution to journalArticle

Shirahige, K, Hori, Y, Shiraishi, K, Yamashita, M, Takahashi, K, Obuse, C, Tsurimoto, T & Yoshikawa, H 1998, 'Regulation of DNA-replication origins during cell-cycle progression', Nature, vol. 395, no. 6702, pp. 618-621. https://doi.org/10.1038/27007
Shirahige K, Hori Y, Shiraishi K, Yamashita M, Takahashi K, Obuse C et al. Regulation of DNA-replication origins during cell-cycle progression. Nature. 1998 Oct 8;395(6702):618-621. https://doi.org/10.1038/27007
Shirahige, Katsuhiko ; Hori, Yuji ; Shiraishi, Katsuya ; Yamashita, Minoru ; Takahashi, Keiko ; Obuse, Chikashi ; Tsurimoto, Toshiki ; Yoshikawa, Hiroshi. / Regulation of DNA-replication origins during cell-cycle progression. In: Nature. 1998 ; Vol. 395, No. 6702. pp. 618-621.
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