Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage.

Published

Journal Article

Structural maintenance of chromosomes (SMC) proteins play important roles in sister chromatid cohesion, chromosome condensation, sex-chromosome dosage compensation, and DNA recombination and repair. Protein complexes containing heterodimers of the Smc1 and Smc3 proteins have been implicated specifically in both sister chromatid cohesion and DNA recombination. Here, we show that the protein kinase, Atm, which belongs to a family of phosphatidylinositol 3-kinases that regulate cell cycle checkpoints and DNA recombination and repair, phosphorylates Smc1 protein after ionizing irradiation. Atm phosphorylates Smc1 on serines 957 and 966 in vitro and in vivo, and expression of an Smc1 protein mutated at these phosphorylation sites abrogates the ionizing irradiation-induced S phase cell cycle checkpoint. Optimal phosphorylation of these sites in Smc1 after ionizing irradiation also requires the presence of the Atm substrates Nbs1 and Brca1. These same sites in Smc1 are phosphorylated after treatment with UV irradiation or hydroxyurea in an Atm-independent manner, thus demonstrating that another kinase must be involved in responses to these cellular stresses. Yeast containing hypomorphic mutations in SMC1 and human cells overexpressing Smc1 mutated at both of these phosphorylation sites exhibit decreased survival following ionizing irradiation. These results demonstrate that Smc1 participates in cellular responses to DNA damage and link Smc1 to the Atm signal transduction pathway.

Full Text

Duke Authors

Cited Authors

  • Kim, S-T; Xu, B; Kastan, MB

Published Date

  • March 1, 2002

Published In

Volume / Issue

  • 16 / 5

Start / End Page

  • 560 - 570

PubMed ID

  • 11877376

Pubmed Central ID

  • 11877376

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.970602

Language

  • eng

Conference Location

  • United States