Checkpoint Responses to DNA Double-Strand Breaks

• Published in: Annual review of biochemistry Vol. 89; no. 1; pp. 103 - 133
• Main Authors: Waterman, David P, Haber, James E, Smolka, Marcus B
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 20-06-2020; Annual Reviews, Inc
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins - chemistry; Ataxia Telangiectasia Mutated Proteins - genetics; Ataxia Telangiectasia Mutated Proteins - metabolism; Cell cycle; Cell Cycle Checkpoints - genetics; checkpoint; Checkpoint Kinase 1 - genetics; Checkpoint Kinase 1 - metabolism; Checkpoint Kinase 2 - genetics; Checkpoint Kinase 2 - metabolism; Chromosomes; Damage; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA Breaks, Double-Stranded; DNA damage; DNA double-strand break; DNA End-Joining Repair; DNA repair; Gene expression; Heredity; Humans; kinases; Lethality; Models, Molecular; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Protein Structure, Secondary; Recombinational DNA Repair; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Yeasts; checkpoint; kinases; cell cycle; DNA double-strand break; DNA repair
• ISSN: 0066-4154; 1545-4509
• DOI: 10.1146/annurev-biochem-011520-104722

Cells confront DNA damage in every cell cycle. Among the most deleterious types of DNA damage are DNA double-strand breaks (DSBs), which can cause cell lethality if unrepaired or cancers if improperly repaired. In response to DNA DSBs, cells activate a complex DNA damage checkpoint (DDC) response that arrests the cell cycle, reprograms gene expression, and mobilizes DNA repair factors to prevent the inheritance of unrepaired and broken chromosomes. Here we examine the DDC, induced by DNA DSBs, in the budding yeast model system and in mammals.