Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway

TLDR

RAD53 and MEC1 are essential genes required for transcriptional and cell‑cycle responses to DNA damage and replication blocks. We propose that this checkpoint pathway is essential for preserving DNA synthetic capacity during replication stress. Our data show that up‑regulation of ribonucleotide reductase suppresses the lethal phenotype of mec1 and rad53 mutants, that Mec1 is more critical than Rad53 for responding to DNA‑synthesis inhibition, and that their loss of survival after transient replication inhibition results from failure to complete chromosome replication rather than premature anaphase entry.

Abstract

RAD53 and MEC1 are essential genes required for the transcriptional and cell cycle responses to DNA damage and DNA replication blocks. We have examined the essential function of these genes and found that their lethality but not their checkpoint defects can be suppressed by increased expression of genes encoding ribonucleotide reductase. Analysis of viable null alleles revealed that Mec1 plays a greater role in response to inhibition of DNA synthesis than Rad53. The loss of survival in mec1 and rad53 null or point mutants in response to transient inhibition of DNA synthesis is not a result of inappropriate anaphase entry but primarily to an inability to complete chromosome replication. We propose that this checkpoint pathway plays an important role in the maintenance of DNA synthetic capabilities when DNA replication is stressed.