Regulation of DNA-replication origins during cell-cycle progression

Katsuhiko Shirahige, Yuji Hori, Katsuya Shiraishi, Minoru Yamashita, Keiko Takahashi, Chikashi Obuse, Toshiki Tsurimoto and Hiroshi Yoshikawa ()
Additional contact information
Katsuhiko Shirahige: Nara Institute of Science and Technology
Yuji Hori: Nara Institute of Science and Technology
Katsuya Shiraishi: Nara Institute of Science and Technology
Minoru Yamashita: Ajinomoto Co. Inc.
Keiko Takahashi: Nara Institute of Science and Technology
Chikashi Obuse: Nara Institute of Science and Technology
Toshiki Tsurimoto: Nara Institute of Science and Technology
Hiroshi Yoshikawa: Nara Institute of Science and Technology

Nature, 1998, vol. 395, issue 6702, 618-621

Abstract: 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 cycle1,2. 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. rad53 is, therefore, involved in the cell's surveillance of S-phase progression4,5. We also find that orc2, which encodes subunit 2 of the origin-recognition complex6,7, is involved in suppression of late origins.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/27007 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:395:y:1998:i:6702:d:10.1038_27007

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/27007

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().