Dynamic targeting of the replication machinery to sites of DNA damage

David A. Solomon, M. Cristina Cardoso, Erik S. Knudsen

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Components of the DNA replication machinery localize into discrete subnuclear foci after DNA damage, where they play requisite functions in repair processes. Here, we find that the replication factors proliferating cell nuclear antigen (PCNA) and RPAp34 dynamically exchange at these repair foci with discrete kinetics, and this behavior is distinct from kinetics during DNA replication. Posttranslational modification is hypothesized to target specific proteins for repair, and we find that accumulation and stability of PCNA at sites of damage requires monoubiquitination. Contrary to the popular notion that phosphorylation on the NH2 terminus of RPAp34 directs the protein for repair, we demonstrate that phosphorylation by DNA-dependent protein kinase enhances RPAp34 turnover at repair foci. Together, these findings support a dynamic exchange model in which multiple repair factors regulated by specific modifications have access to and rapidly turn over at sites of DNA damage.

Original languageEnglish (US)
Pages (from-to)455-463
Number of pages9
JournalJournal of Cell Biology
Volume166
Issue number4
DOIs
Publication statusPublished - Aug 16 2004

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Keywords

  • Cisplatin
  • Foci
  • FRAP
  • Proliferating cell nuclear antigen
  • Replication protein A

ASJC Scopus subject areas

  • Cell Biology

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