SMC1 phospho S957 Antibody

Background

Structural maintenance of chromosomes (SMC) proteins play important roles in sister chromatid cohesion, chromosome condensation, sex-chromosome dosage compensation, and DNA recombination and repair (DNA damage). Protein complexes containing heterodimers of the SMC1 and SMC3 proteins have been implicated specifically in both sister chromatid cohesion and DNA recombination.  ATM, a protein kinase belonging to the phosphatidylinositol 3-kinase family that regulates cell cycle checkpoints and DNA recombination and repair, phosphorylates SMC1 protein after ionizing irradiation. ATM protein kinase 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 protein kinase 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 protein kinase signal transduction pathway.