Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization

Takehiko Usui, Steven Foster, John H. J. Petrini

Research output: Contribution to journal › Article

42 Citations (Scopus)

Abstract

Oligomeric assembly of Brca1 C-terminal (BRCT) domain-containing mediator proteins occurs at sites of DNA damage. However, the functional significance and regulation of such assemblies are not well understood. In this study, we defined the molecular mechanism of DNA-damage-induced oligomerization of the S. cerevisiae BRCT protein Rad9. Our data suggest that Rad9's tandem BRCT domain mediates Rad9 oligomerization via its interaction with its own Mec1/Tel1-phosphorylated SQ/TQ cluster domain (SCD). Rad53 activation is unaffected by mutations that impair Rad9 oligomerization, but checkpoint maintenance is lost, indicating that oligomerization is required to sustain checkpoint signaling. Once activated, Rad53 phosphorylates the Rad9 BRCT domain, which attenuates the BRCT-SCD interaction. Failure to phosphorylate the Rad9 BRCT results in cytologically visible Rad9 foci. This suggests a feedback loop wherein Rad53 activity and Rad9 oligomerization are regulated to tune the DNA-damage response.
Original languageEnglish
Pages (from-to)147-159
Number of pages13
JournalMolecular Cell
Volume33
Issue number2
DOIs
Publication statusPublished - 30 Jan 2009

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Oligomerization
DNA Damage
Maintenance
DNA
Proteins
Protein C
Saccharomyces cerevisiae
Mutation
Chemical activation
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Bibliographical note

Open Archive

Keywords

  • DNA
  • Signalling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization. / Usui, Takehiko ; Foster, Steven; Petrini, John H. J.

In: Molecular Cell, Vol. 33, No. 2, 30.01.2009, p. 147-159.

Research output: Contribution to journal › Article

Usui, T, Foster, S & Petrini, JHJ 2009, 'Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization' Molecular Cell, vol. 33, no. 2, pp. 147-159. https://doi.org/10.1016/j.molcel.2008.12.022
Usui T, Foster S, Petrini JHJ. Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization. Molecular Cell. 2009 Jan 30;33(2):147-159. https://doi.org/10.1016/j.molcel.2008.12.022
Usui, Takehiko ; Foster, Steven ; Petrini, John H. J. / Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization. In: Molecular Cell. 2009 ; Vol. 33, No. 2. pp. 147-159.
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