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closeore about ORF-ORCs
Posted by raramayo on 02 Mar 2010 at 22:46 GMT
The manuscript by Erica Shor and colleagues was the topic of our Chromosome Biology Journal Club. The data presented is very strong and raises several intriguing questions regarding the biological function of these newly-identified ORC-ORFs sequences. The authors mentioned that "A shared feature of all yeast origins of replication is the ARS Consensus Sequence (ACS)—an AT-rich sequence necessary but not sufficient for ORC binding."
Because ORC-ORFs can recruit the ORC complex and the ORC complex includes at least one protein subunit known to contain an AT-Hook domain [1], suggest that the AT composition of these ORC-ORFs should not only be similar to the AT composition of the confirmed ARS, but also significantly higher from that of the DNA sequences corresponding to that of all the ORFs in the genome.
We wandered if the authors had actually determined the GC composition of these newly identified regions. Indeed a quick calculation of the GC composition of all 337 Confirmed ARS in the yeast genome reveals that they are 32.31% GC-rich (± 0.0563). We found that the GC composition of the ORC-ORFs is 45.19 (± 0.0387), which is significantly different from that of the ARS. In addition, we also found that the GC composition of all ORFs and those corresponding to the ORC-ORFs are not significantly different (45.19 (± 0.0387) versus 40.10% (± 0.0407)). This observation accentuates even further the importance of the main finding of the paper as it discards AT-richness as a main factor controlling the affinity of ORC to these regions. The biological role of not only these sequences but also that of the AT-Hook domains present in ORC remains to be determined.
We also looked if the length of the DNA and protein sequences corresponding to all ORFs in the genome were significantly different from that of the corresponding ORC-ORFs regions. For DNA we found that mean length for ORF in the yeast genome is (1,369 bp (± 1,158 bp) versus 1,306 (± 613) for ORC-ORFs regions. For proteins we found that mean length for ORF in the yeast genome is 450 aar (± 368) versus 434 aar (± 204) for ORC-ORFs regions. We consider these numbers to be equivalent.
1. Duncker, B.P., I.N. Chesnokov, and B.J. McConkey, The origin recognition complex protein family. Genome Biol, 2009. 10(3): p. 214.
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Rodolfo Aramayo, Michael Polymenis and the Chromosome Biology Journal Club (Kara Boltz, Jindang Cai, Nehemiah Cox , Scott Hoose, Rachel Jordan, Aldrin Lugena, Ryan Millimaki, Ana Suescun, Kelly Williamson, Michelle Yeoman)
RE: ore about ORF-ORCs
erikashor replied to raramayo on 03 Mar 2010 at 01:54 GMT
Thank you for your comment. We also checked GC content and length and found no significant differences between ORF-ORC genes and the genome as a whole. We favor the idea that ORC associates with these genes not via direct DNA binding but rather through protein-protein interactions with chromatin or transcription complexes, although we don't have any concrete evidence for or against it yet.