Structural maintenance of chromosome I (Smcl) is a multifunctional protein, which has been implicated in sister chromatid cohesion, DNA recombination and repair, and the activation of cell cycle checkpoints by ionizing radiation, ultraviolet light, and other genotoxic agents. In order to identify the proteins that interact with Smcl, we conducted the Tandem affinity purification (TAP) technique and analyzed the Smcl-interacting proteins via MALDI-TOF mass spectrometry. We identified minichromosome maintenance 7 (Mcm7), an essential component of the pre-replication complex, as a novel Smcl-interacting protein. Co-immunoprecipitation revealed an interaction occurring between Smcl and Mcm7, both in vitro and in vivo. Using a GST pull-down assay, we determined that Smel interacts physically with Mcm7 via its N-terminal and hinge regions, and Mcm7 interacts with Smcl via its middle region. Interestingly, we also discovered that Strict interacts with other DNA replication proteins, including Mcm6, RFCI, and DNA polymerase Ot. These results suggest that a functional link exists between the cohesin complex and DNA replication proteins. (c) 2006 Elsevier Inc. All rights reserved.