S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex

Yuki Katou, Yutaka Kanoh, Masashige Bando, Hideki Noguchi, Hirokazu Tanaka, Toshihiko Ashikari, Katsunori Sugimoto and Katsuhiko Shirahige ()
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Yuki Katou: RIKEN Genomic Science Center
Yutaka Kanoh: RIKEN Genomic Science Center
Masashige Bando: RIKEN Genomic Science Center
Hideki Noguchi: RIKEN Genomic Science Center
Hirokazu Tanaka: RIKEN Genomic Science Center
Toshihiko Ashikari: Institute for Advanced Technology, Suntory Limited
Katsunori Sugimoto: Nagoya University Graduate School of Science
Katsuhiko Shirahige: RIKEN Genomic Science Center

Nature, 2003, vol. 424, issue 6952, 1078-1083

Abstract: Abstract The checkpoint regulatory mechanism has an important role in maintaining the integrity of the genome1,2,3,4,5. This is particularly important in S phase of the cell cycle, when genomic DNA is most susceptible to various environmental hazards3,6,7. When chemical agents damage DNA, activation of checkpoint signalling pathways results in a temporary cessation of DNA replication. A replication-pausing complex is believed to be created at the arrested forks to activate further checkpoint cascades, leading to repair of the damaged DNA. Thus, checkpoint factors are thought to act not only to arrest replication but also to maintain a stable replication complex at replication forks6,7,8,9. However, the molecular mechanism coupling checkpoint regulation and replication arrest is unknown. Here we demonstrate that the checkpoint regulatory proteins Tof1 and Mrc1 interact directly with the DNA replication machinery in Saccharomyces cerevisiae. When hydroxyurea blocks chromosomal replication, this assembly forms a stable pausing structure that serves to anchor subsequent DNA repair events.

Date: 2003
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DOI: 10.1038/nature01900

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