Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle

Hiroaki Kato, Fujihiko Matsunaga, Shota Miyazaki, Ling Yin, Gennaro D'urso, Katsunori Tanaka, Yota Murakami

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The six-subunit origin recognition complex (ORC) acts as a landing pad for factors that initiate DNA replication by binding to replication origins. In addition, ORC is involved in other processes such as transcriptional gene silencing and sister chromatid cohesion in Saccharomyces cerevisiae. However, whether these functions of ORC are specific to Saccharomyces cerevisiae or are shared by the ORC of other organisms is currently unclear. Analysis of two temperature-sensitive alleles of the fifth ORC subunit of Schizosaccharomyces pombe, orc5-H19 and orc5-H37, indicates that Orc5 of Schizosaccharomyces pombe has similar multiple functions to those of Orc5 of Saccharomyces cerevisiae. The orc5-H19 cells were defective in DNA replication initiation, and execution point analysis of this mutant revealed that ORC functions before metaphase to prepare for the initiation of replication in the next cell cycle. The orc5-H37 cells seemed to complete DNA synthesis but were arrested before entering M phase. In both mutants, the rads-chk1 checkpoint was activated to prevent mitosis, suggesting that this checkpoint pathway monitors the functional integrity of ORC. In addition, orc5-H37 cells showed premature separation of sister chromatids, which resulted in cell growth being dependent on the mad2-dependent spindle checkpoint. Consistently, this mutant showed a defect in the loading of Rad21, a cohesin component. Based on these observations, we propose that Orc5 has at least two distinct functions that can be separated genetically. Taken together, our results provide further support for the idea that ORC plays multiple functions during the cell cycle.

Original languageEnglish
Pages (from-to)1085-1096
Number of pages12
JournalCell Cycle
Volume7
Issue number8
StatePublished - Apr 15 2008

Fingerprint

Origin Recognition Complex
Schizosaccharomyces
Genomic Instability
Cell Cycle
Genes
Cells
Maintenance
Yeast
Saccharomyces cerevisiae
Chromatids
DNA Replication
DNA
Replication Origin
Cell growth
Gene Silencing
Metaphase
Landing
Mitosis
Cell Division
Alleles

Keywords

  • Checkpoint
  • Chromosome dynamics
  • Cohesin
  • DNA replication
  • Fission yeast
  • Origin recognition complex
  • Sister chromatid cohesion

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Kato, H., Matsunaga, F., Miyazaki, S., Yin, L., D'urso, G., Tanaka, K., & Murakami, Y. (2008). Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle. Cell Cycle, 7(8), 1085-1096.

Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle. / Kato, Hiroaki; Matsunaga, Fujihiko; Miyazaki, Shota; Yin, Ling; D'urso, Gennaro; Tanaka, Katsunori; Murakami, Yota.

In: Cell Cycle, Vol. 7, No. 8, 15.04.2008, p. 1085-1096.

Research output: Contribution to journalArticle

Kato, H, Matsunaga, F, Miyazaki, S, Yin, L, D'urso, G, Tanaka, K & Murakami, Y 2008, 'Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle', Cell Cycle, vol. 7, no. 8, pp. 1085-1096.
Kato, Hiroaki ; Matsunaga, Fujihiko ; Miyazaki, Shota ; Yin, Ling ; D'urso, Gennaro ; Tanaka, Katsunori ; Murakami, Yota. / Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle. In: Cell Cycle. 2008 ; Vol. 7, No. 8. pp. 1085-1096.
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