Abstract

Completion of DNA replication before mitosis is essential for genome stability and cell viability. Cellular controls called checkpoints act as surveillance mechanisms capable of detecting errors and blocking cell cycle progression to allow time for those errors to be corrected. An important question in the cell cycle field is whether eukaryotic cells possess mechanisms that monitor ongoing DNA replication and make sure that all chromosomes are fully replicated before entering mitosis, that is whether a replication-completion checkpoint exists. From recent studies with smc5–smc6 mutants it appears that yeast cells can enter anaphase without noticing that replication in the ribosomal DNA array was unfinished. smc5–smc6 mutants are proficient in all known cellular checkpoints, namely the S phase checkpoint, DNA-damage checkpoint, and spindle checkpoint, thus suggesting that none of these checkpoints can monitor the presence of unreplicated segments or the unhindered progression of forks in rDNA. Therefore, these results strongly suggest that normal yeast cells do not contain a DNA replication-completion checkpoint.

Highlights

  • The cell cycle is the sequence of events by which cells make a copy of themselves, giving rise to two daughter cells at division

  • An important question in the cell cycle field is whether eukaryotic cells possess mechanisms that monitor ongoing DNA replication and make sure that all chromosomes are fully replicated before entering mitosis, that is whether a replication-completion checkpoint exists

  • From recent studies with smc5–smc6 mutants it appears that yeast cells can enter anaphase without noticing that replication in the ribosomal DNA array was unfinished. smc5–smc6 mutants are proficient in all known cellular checkpoints, namely the S phase checkpoint, DNA-damage checkpoint, and spindle checkpoint, suggesting that none of these checkpoints can monitor the presence of unreplicated segments or the unhindered progression of forks in rDNA

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Summary

Cell cycle and checkpoints

The cell cycle is the sequence of events by which cells make a copy of themselves, giving rise to two daughter cells at division. The most important events in the cell cycle are the faithful replication and segregation of all chromosomes In eukaryotic cells these events are separated in time, with every round of DNA replication in S phase preceding chromosome segregation in M phase. The cell cycle is often viewed as a precise ticking mechanism that drives mitotic cells from one phase into the one. In order to adapt to changes in the timing needed to finish cell cycle events, all eukaryotic organisms have special mechanisms, known as cell cycle checkpoints. These prevent cells from leaving one stage until a particular event has taken place, or a particular condition has been satisfied. Failure to delay the cell cycle under some certain circumstances can have disastrous consequences, from genomic instability to the death of the organism

Genome replication
Replication Fork arrest and the S phase checkpoint

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