Tetramer disrupters

First, the researchers confirmed that the p subunit s association with the a subunit is disrupted if the T1 domain is removed. The X-ray crystallographic structure of the assembled TI4P4 complex showed why this is the case. The structure shows that large flat surfaces of the p subunit interact with four prominent loops—called contact loops—that extend from the T1 tetramer s... 

Santisteban, M.S., Arents, G., Moudrianakis, E.N., and Smith, M.M. (1997) Histone octamer function in vivo mutations in the dimer-tetramer interfaces disrupt both gene activation and repression. EMBO J. 16, 2493-2506. 

The model of Fig. IB is taken from a review by van Holde et al. [3] which I refer to as the disruptive model. In this model the polymerase causes conditions (step A) which promote not only the displacement of the entry site H2A, H2B dimer from DNA, but also from the H3, H4 tetramer (step B). As a result of this disruption, the polymerase is free to transcribe through the tetramer alone without a general displacement from its associated DNA (step C). The H2A, H2B dimer is now free to reassociate to the vacated entry site (step D) to re-establish contacts with both the DNA and the H3, H4 tetramer. As transcription proceeds into the exit site H2A, H2B dimer, these proteins are now displaced from both the DNA and the H3, H4 tetramer in a similar manner as the entry site H2A, H2B dimer (step E). A positive feature with regard to this model is that by displacement of H2A, H2B, the polymerase is able to transcribe the DNA with half the histones displaced prior to transcription. Therefore both models, spooling and disruptive , describe mechanisms which would favorably enhance the process of transcription. Support for the disruptive model comes from the substantial in vivo information which suggests that nucleosomes undergo substantial disruption during transcription, as was described in the previous section. Of particular note are those observations which indicate that a discrete population of H2A, H2B... 

Hb Memphis substitutes one uncharged polar residue for another of similar size on the surface Hb Bibba substitutes a Pro for a Leu involved in an a helix Hb Milwaukee substitutes a Glu for a Val Hb Providence substitutes an Asn for a Lys that normally projects into the central cavity of the tetramer Hb Philly substitutes a Phe for a T r, disrupting hydrogen bonding at the au8i interface... 

Why are p53 mutations so common First, p53 binds to DNA as a tetramer, and dominant negative mutants are able to disrupt the formation or activity of... 

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