The Origin Recognition Complex (ORC) is a six-subunit protein important for the initiation of DNA replication in eukaryotic cells. Orc6 is the smallest and the least conserved among ORC subunits. It is required for the DNA replication but also has a function in cytokinesis in metazoan species. In both Drosophila and human cells, Orc6 has been implicated in coordinating cytokinesis with pre-RC formation and chromosome segregation, a role that it performs independently of the rest of the complex. However, the mechanisms of Orc6 action in these processes are not clear. Solving the structure of Orc6 would be very beneficial to study the functions of this important protein.

Professor Yingfang Liu at the Institute of Biophysics, Chinese Academy of Sciences and his colleagues at University of Alabama at Birmingham carried out studies on the structure of Orc6. Their earlier model predicted that the N-terminal replication domain of metazoan Orc6 might have a fold similar to the helical domain of transcription factor TFIIB. To test this model and to characterize the functions of Orc6 further, they recently determined the structure of human Orc6 middle region (Orc6-M), which includes amino acids 94–187. This domain has an overall fold similar to the corresponding helical domain of transcription factor TFIIB. Based on these findings, a model of Orc6 binding to DNA is produced. They identified amino acids of Orc6 which are directly involved in DNA binding. Alterations of these amino acids abolish DNA binding ability of Orc6 and also result in reduced levels of DNA replication in vitro and in cultured cells. Their data indicate that Orc6 is one of the DNA binding subunits of ORC in metazoan species. They proposed that Orc6 may participate in positioning of ORC at the origins of DNA replication similar to the role of TFIIB in positioning transcription preinitiation complex at the promoter.

This new work on human Orc6 structure was published in the latest issue of PNAS (2011,108(18):7373-7378) and titled “Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB”.