User:Cameron Ball/Sandbox 1: Difference between revisions
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==Mechanism== | ==Mechanism== | ||
Two possible (non-mutually exclusive) mechanisms were originally proposed to explain it's activity; The "differential binding affinity" model (DBA), where RTP's different affinity for the A and B sites gives rise to the polarity, and the "conformational change" model, where the polarity is a result of different conformations assumed by each RTP dimer on each half site.<ref>Duggin, I.G., Mathews, J.M., Dixon, N.E., Wake, R.G., Mackay, J.P., A Complex Mechanism Determines Polarity of DNA Replication Fork Arrest by the Replication Terminator Complex of ''Bacillus subtilis'' 2005 The Journal of Biological Chemistry, 280, 13105-13113.</ref> Recent data has shown that RTP-Ter contact is not sufficient to cause arrest, suggesting there is more to each proposed model<ref>Duggin, I.G., Mathews, J.M., Dixon, N.E., Wake, R.G., Mackay, J.P., A Complex Mechanism Determines Polarity of DNA Replication Fork Arrest by the Replication Terminator Complex of ''Bacillus subtilis'' 2005 The Journal of Biological Chemistry, 280, 13105-13113.</ref><ref> Kaplan, D.L and Bastia, D, Mechanisms of polar arrest of a replication fork, Molecular Microbiology 2009:72:2), pp 279-285 </ref>. Additionally, in 2006 Ian Duggin showed that the fork arrest efficiency of RTP can be lowered while maintaining the same RTP-DNA binding affinity by attaching short peptides to RTP's non-permissive face. These peptides block any protein-protein interaction with the approaching replisome unit <ref> Duggin, I.G., DNA replication fork arrest by the Bacillus subtilis RTP-DNA complex involves a mechanism that is independent of the affinity of RTP-DNA binding ''J Mol Biol'' '''361:'''1-6</ref> suggesting that RTP is not simply acting as a directional block, but that there is some protein-protein interaction occuring that has yet to be elucidated. | Two possible (non-mutually exclusive) mechanisms were originally proposed to explain it's activity; The "differential binding affinity" model (DBA), where RTP's different affinity for the A and B sites gives rise to the polarity, and the "conformational change" model, where the polarity is a result of different conformations assumed by each RTP dimer on each half site.<ref>Duggin, I.G., Mathews, J.M., Dixon, N.E., Wake, R.G., Mackay, J.P., A Complex Mechanism Determines Polarity of DNA Replication Fork Arrest by the Replication Terminator Complex of ''Bacillus subtilis'' 2005 The Journal of Biological Chemistry, 280, 13105-13113.</ref> Recent data has shown that RTP-Ter contact is not sufficient to cause arrest, suggesting there is more to each proposed model<ref>Duggin, I.G., Mathews, J.M., Dixon, N.E., Wake, R.G., Mackay, J.P., A Complex Mechanism Determines Polarity of DNA Replication Fork Arrest by the Replication Terminator Complex of ''Bacillus subtilis'' 2005 The Journal of Biological Chemistry, 280, 13105-13113.</ref><ref> Kaplan, D.L and Bastia, D, Mechanisms of polar arrest of a replication fork, Molecular Microbiology 2009:72:2), pp 279-285 </ref>. Additionally, in 2006 Ian Duggin showed that the fork arrest efficiency of RTP can be lowered while maintaining the same RTP-DNA binding affinity by attaching short peptides to RTP's non-permissive face. These peptides block any protein-protein interaction with the approaching replisome unit <ref> Duggin, I.G., DNA replication fork arrest by the Bacillus subtilis RTP-DNA complex involves a mechanism that is independent of the affinity of RTP-DNA binding ''J Mol Biol'' '''361:'''1-6</ref> suggesting that RTP is not simply acting as a directional block, but that there is some protein-protein interaction occuring that has yet to be elucidated. | ||
To summarise, one RTP dimer binds at the B-site and deforms the DNA in such a way that binding of another dimer at the A site is favourable, and the different affinities of the two sites for RTP results in non symmetrical binding. When a polymerase unit approaches the RTP from the permissive face (A site) the RTP complex is dislodged and replication continues. If the polymerase approached from the non permissive face the stronger interaction of the B-site with RTP, in combination with a protein-protein interaction (possibly with the approaching helicase, halting DNA melting) arrests DNA replication. | |||
==Comparison of Tus and RTP== | ==Comparison of Tus and RTP== | ||
