What is the effect of acetylation acetylation on Orc1p`s silencing function? Until now, Sir1p`s recruitment for silencers was considered Orc1p`s exclusive task in silencing. However, genetic data indicate that the ORC has additional silencing functions. In particular, telomien silencing is entirely dependent on orC, while it is not affected by the suppression of SIR1 (12), which shows that orC has a telomere silencing function. It is interesting to note that N`a acetylation did not affect Orc1p`s ability to interact with sir1p, a finding that occurred with the previous observation, consistent with the previous observation, that SIR1 overexpression suppressed the HML silencing defect (45). This is why we propose that the term Orc1p-Amino interacts with an as yet unidentified silencing protein, which works mainly in telomere silencing, and that this interaction requires an acetylation of Orc1p by NatA. This view is supported by our finding that the ORC link to telomeres was not inhibited by the absence of N-acetyllation (see below). Crystallographic data show that Orc1p`s extreme N-Endus is exposed to the surface of the protein in a different structure from Sir1p`s field of interaction (54), making it a potential interaction module for another protein. Given the great resemblance between Orc1p and Sir3p N termini, it is interesting to note that we also found sir3p that it was acetylé by NatA. One possibility is that the acetyled orc1p and Sir3p both interact with the same hypothetical silencing factor. This new interaction partner can explicitly recognize the Orc1p and/or Sir3p terminus N in its acetylle form. Priority for protein interactions related to modification is given by bromine and chromodomain proteins, which prefer to retain specific residues of acetyled or methyle histones (25).
1309.339. (UCC 9-339) Priority under subordination. Nothing in this chapter excludes the subordination by convention of a priority recipient. How does natA acetylation affect silencing? Of course, NatA has many cellular targets, which is reflected in the pleiotropic phenotypes of nat1 or ard1 mutants, but few substrates are relevant to silencing. Non-acetych orc1 mutants show the same amount of reckless repression as nat1, arguing that NatA`s orc1p acetylation plays a decisive role in telomere silencing. In hm loci, nat1- has a stronger derepression than non-Macaques Orc1 mutants. One explanation is that thelomero silencing is less robust than HM silencing and can therefore be more easily disturbed by the lack of Orc1p N acetylation. In this context, another orcmutation, orc5-1, also has more effect on telomere silencing than HM silencing (12, 29). Another possibility is that Orc1p N acetylation plays a minor role in HM silencing and, therefore, natA acts primarily on other silencing factors.
In keeping with this, the pristine Sir3 mutant showed a powerful HM-Silencing phenotype. It is also possible that NatA has several other targets among the silencing components. One scenario is that additional ORC sub-units are natA objectives. This notion is supported by an alternative interpretation of our results related to the silent circuit. As the orC`s function is to recruit Orc1p and thus Sir1p to the silencer, Orc1p`s direct antedering can bypass the need for a correct ORC mount to convey silence.
