Dial 9–1–1 for DNA damage: the Rad9–Hus1–Rad1 (9–1–1) clamp complex

Genotoxic stress activates checkpoint signaling pathways that block cell cycle progression, trigger apoptosis, and regulate DNA repair. Studies in yeast and humans have shown that Rad9, Hus1, Rad1, and Rad17 play key roles in checkpoint activation. Three of these proteins–Rad9, Hus1, and Rad1–intera...

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Bibliographic Details
Published in:DNA Repair 2004-08, Vol.3 (8), p.1009-1014
Main Authors: Parrilla-Castellar, Edgardo R., Arlander, Sonnet J.H., Karnitz, Larry
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell Cycle
Cell Cycle Proteins - physiology
Cell Division
Checkpoint
DNA - chemistry
DNA - genetics
DNA Damage
DNA Repair
DNA Repair Enzymes
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Endonucleases - physiology
Fungal Proteins - metabolism
G2 Phase
Humans
Hus1
Models, Biological
Protein Binding
Rad1
Rad17
Rad9
Replication Protein C
S Phase
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins
Schizosaccharomyces - physiology
Schizosaccharomyces pombe Proteins
Signal Transduction
Time Factors
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Summary:Genotoxic stress activates checkpoint signaling pathways that block cell cycle progression, trigger apoptosis, and regulate DNA repair. Studies in yeast and humans have shown that Rad9, Hus1, Rad1, and Rad17 play key roles in checkpoint activation. Three of these proteins–Rad9, Hus1, and Rad1–interact in a heterotrimeric complex (dubbed the 9-1-1 complex), which resembles a PCNA-like sliding clamp, whereas Rad17 is part of a clamp-loading complex that is related to the PCNA clamp loader, replication factor-C (RFC). In response to genotoxic damage, the 9-1-1 complex is loaded around DNA by the Rad17-containing clamp loader. The DNA-bound 9-1-1 complex then facilitates ATR-mediated phosphorylation and activation of Chk1, a protein kinase that regulates S-phase progression, G2/M arrest, and replication fork stabilization. In addition to its role in checkpoint activation, accumulating evidence suggests that the 9-1-1 complex also participates in DNA repair. Taken together, these findings suggest that the 9-1-1 clamp is a multifunctional complex that is loaded onto DNA at sites of damage, where it coordinates checkpoint activation and DNA repair.
ISSN:1568-7864
1568-7856
DOI:10.1016/j.dnarep.2004.03.032