Dial 9-1-1 for DNA damage

The Rad9-Hus1-Rad1 (9-1-1) clamp complex

Edgardo R. Parrilla-Castellar, Sonnet J H Arlander, Larry M Karnitz

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1009-1014
Number of pages6
JournalDNA Repair
Volume3
Issue number8-9
DOIs
StatePublished - Aug 2004

Fingerprint

Clamping devices
DNA Repair
DNA Damage
Proliferating Cell Nuclear Antigen
DNA
Replication Protein C
Chemical activation
Loaders
Repair
S Phase
Cell Cycle
Yeasts
Phosphorylation
Apoptosis
Yeast
Protein Kinases
Stabilization
Cells

Keywords

  • Checkpoint
  • DNA damage
  • DNA repair
  • Hus1
  • Rad1
  • Rad17
  • Rad9

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Dial 9-1-1 for DNA damage : The Rad9-Hus1-Rad1 (9-1-1) clamp complex. / Parrilla-Castellar, Edgardo R.; Arlander, Sonnet J H; Karnitz, Larry M.

In: DNA Repair, Vol. 3, No. 8-9, 08.2004, p. 1009-1014.

Research output: Contribution to journalArticle

Parrilla-Castellar, Edgardo R. ; Arlander, Sonnet J H ; Karnitz, Larry M. / Dial 9-1-1 for DNA damage : The Rad9-Hus1-Rad1 (9-1-1) clamp complex. In: DNA Repair. 2004 ; Vol. 3, No. 8-9. pp. 1009-1014.
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