Surviving the breakup: the DNA damage checkpoint.

  title={Surviving the breakup: the DNA damage checkpoint.},
  author={Jacob C. Harrison and James E. Haber},
  journal={Annual review of genetics},
In response to even a single chromosomal double-strand DNA break, cells enact the DNA damage checkpoint. This checkpoint triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. This mechanism helps prevent the segregation of damaged or mutated chromosomes and thus promotes genomic stability. Recent work has elucidated the molecular mechanisms underlying several critical steps in checkpoint activation, notably the recruitment of the upstream… 

Figures and Tables from this paper

Cell cycle re-entry mechanisms after DNA damage checkpoints: Giving it some gas to shut off the breaks!
Recent reports in which molecular mechanisms underlying checkpoint silencing at the G2/M transition are elucidated are reviewed, showing that cell cycle kinases and the DNA damage checkpoint kinases appear to reciprocally control each other.
DNA damage checkpoints: from initiation to recovery or adaptation.
Eukaryotic DNA damage checkpoint activation in response to double-strand breaks
This review focuses on the Cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA damage and preserve genome stability in eukaryotic cells.
Orchestration of the DNA damage checkpoint response through the regulation of the protein kinase Rad53.
The study of Rad53 at the molecular and atomic level revealed that in addition to being regulated through a complex network of protein-protein interactions, Rad53 autophosphorylation is orchestrated by a mechanism of dimerization, activation segment phosphorylation via Aloop exchange, as well as through an autoinhibition mechanism regulated by a specific αhelical region at the C-terminal extremity of its kinase domain.
Checkpoint Responses to DNA Double-Strand Breaks.
The DDC, induced by DNA DSBs, in the budding yeast model system and in mammals is examined, which arrests the cell cycle, reprograms gene expression, and mobilizes DNA repair factors to prevent the inheritance of unrepaired and broken chromosomes.
DNA damage tolerance: a double-edged sword guarding the genome.
The replication stress induced DNA damage-signaling cascade, the stabilization and rescue of stalled replication forks by the DDT pathway and the effect of theDDT pathway on cancer are discussed.
The Influence of Histone Chaperones and Histone Modifying Proteins in Regulating the DNA Damage Checkpoint
The hypothesis proposed in this thesis is that dissociating H3-H4 from Asf1 is necessary to allow Asf 1 to interact and sequester Rad53 following repair, thus deactivating the checkpoint and facilitating recovery.
Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair
Recent findings are reviewed and insight is provided on how proteins that regulate cell cycle progression affect DSB repair, and, conversely, howprotein that repair DSBs affectcell cycle progression.
Recovery from the DNA Replication Checkpoint
The term “checkpoint recovery" is used to describe the pathways responsible for the inactivation of checkpoint signaling and cell cycle re-entry after the initial stress has been alleviated and the restart of stalled replication forks during recovery from replication stress.


DNA structure dependent checkpoints as regulators of DNA repair.
Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints.
The molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed and apoptosis, which eliminates heavily damaged or seriously deregulated cells, is analyzed.
Sensing, signaling, and responding to DNA damage: Organization of the checkpoint pathways in mammalian cells
  • Lei Li, L. Zou
  • Biology
    Journal of cellular biochemistry
  • 2005
Current models of the DNA damage and replication checkpoints are discussed and recent advances in the field are highlighted, revealing the increasing complexity of the checkpoint control of the cell cycle.
G2 damage checkpoints: what is the turn-on?
Single-stranded DNA, a result of stalled DNA replication or processing of chromosomal lesions, appears to be central to the activation of ATR and phosphorylates the C-terminus of Chk1, activating it to enforce a block to mitotic entry.
Arrest, adaptation, and recovery following a chromosome double-strand break in Saccharomyces cerevisiae.
Although much of the network of interacting proteins is conserved from yeast to mammals, damage-induced arrest in budding yeast appears to be different from damage- induced arrest in both mammalian cells and fission yeast.
Checkpoint Adaptation Precedes Spontaneous and Damage-Induced Genomic Instability in Yeast
The spontaneous and X-ray-induced frequencies of chromosome loss, translocations, and a repair process called break-induced replication occur at significantly reduced rates in adaptation-defective mutants, which indicates that these events occur after a cell has first arrested at the checkpoint and then adapted to that arrest.
The Checkpoint Protein Rad24 of Saccharomyces cerevisiae Is Involved in Processing Double-Strand Break Ends and in Recombination Partner Choice
In rad24 mutants, processing of the broken ends is delayed and protracted, resulting in extended kinetics of DSB repair and in cell death, which affects recombination partner choice by a mechanism dependent on the length of the interacting homologous donor sequences.
Resisting Arrest: Recovery from Checkpoint Arrest Through Dephosphorylation of Chk1 by PP1
The finding that the Schizosaccharomyces pombe type 1 phosphatase (PP1) Dis2 dephosphorylates the checkpoint effector kinase Chk1 occurs on a site phosphorylated by the ATR homologue Rad3 in response to DNA damage, and results in Chk 1 inactivation and checkpoint release is discussed.
Damage in transition.