Abstract
During meiosis, high levels of recombination initiated by DNA double-strand breaks (DSBs) occur only after DNA replication. However, how DSB formation is coupled to DNA replication is unknown. We examined several DNA replication proteins for a role in this coupling in Schizosaccharomyces pombe, and we show that ribonucleotide reductase, the rate-limiting enzyme of deoxyribonucleotide synthesis and the target of the DNA synthesis inhibitor hydroxyurea (HU) is indirectly required for DSB formation linked to DNA replication. However, in cells in which the function of the DNA-replication-checkpoint proteins Rad1p, Rad3p, Rad9p, Rad17p, Rad26p, Hus1p, or Cds1p was compromised, DSB formation occurred at similar frequencies in the absence or presence of HU. The DSBs in the HU-treated mutant cells occurred at normal sites and were associated with recombination. In addition, Cdc2p is apparently not involved in this process. We propose that the sequence of meiotic S phase and initiation of recombination is coordinated by DNA-replication-checkpoint proteins.
MeSH Terms
Cell Cycle Proteins/genetics,metabolism
DNA Replication
Genes, cdc
Hydroxyurea/metabolism
Meiosis/physiology
Nucleic Acid Synthesis Inhibitors/metabolism
Recombination, Genetic
Schizosaccharomyces/cytology,physiology
Schizosaccharomyces pombe Proteins/genetics,metabolism
Chemicals
Cell Cycle Proteins
Nucleic Acid Synthesis Inhibitors
Schizosaccharomyces pombe Proteins
Hydroxyurea
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tonami Yuko
Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Murakami Hiroshi
Shirahige Katsuhiko
Nakanishi Makoto
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