J. Biol. Chem., Vol. 283, Issue 28, 99933, July 11, 2008
A Double Dose of Structure Maintenance of Chromosome Phosphorylation
In response to ionizing radiation, cells activate an intra-S phase checkpoint to halt DNA synthesis and prevent replication of damaged DNA. One major component that activates this checkpoint is the protein structure maintenance of chromosome 1 (SMC1), which becomes phosphorylated following radiation damage. As SMC1 associates with several other proteins to form the cohesion complex, which is indispensable for proper chromosomal metabolism, Hao Luo and colleagues tested if any other members of this complex are involved in the intra-S phase checkpoint in this Paper of the Week. Using mass spectrometry analysis they discovered that the SMC3 protein was also phosphorylated at two different serines. However, although Ser-1083 phosphorylation was radiation-induced like SMC1, the Ser-1067 site, phosphorylated by the CK2 kinase, was constitutive. In addition, a S1067A mutant weakened the phosphorylation of Ser-1083, suggesting that this constitutive site "primes" SMC3 for the second phosphorylation. This interesting discovery provides the first example of a regulatory site for ionizing radiation (IR) damage that's not induced by radiation and suggests that non-induced protein phosphorylations may play important roles in DNA damage checkpoints.
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One of the two phosphorylation sites on the cohesion complex protein SMC3 as identified by MS/MS analysis.
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FOOTNOTES
See referenced article, J. Biol. Chem. 2008, 283, 19176-19183 

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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.