Nicholas Dyson

..These results show that dE2F is required at multiple stages of development and suggest that E2F may have an important function in post-mitotic cells in addition to its role during cell proliferation...

..These results provide the first in vivo evidence that p107 and Rb have overlapping functions in some tissues of the developing and adult mouse...

..These findings indicate that in normal mammalian cells, the onset of DNA synthesis is coordinately regulated at a small number of previously unrecognized perinucleolar sites that are selected in early G(1)-phase...

..Furthermore, because many cancer therapies act by damaging DNA, these findings also have implications for the treatment of tumors in which pRB is inactivated...

..By comparing the genetic requirements of DB-pRB repression in yeast to those of other DB-repressor fusions, we can suggest a mechanism by which pRB recruits histone deacetylase activity...

..These data support the notion that the pRB-binding domain of E1A contains at least two functional elements...

..In this review, we will discuss these recent developments and describe how they are beginning to shape a new and revised picture of the E2F transcriptional program...

..Thus, dDP is not essential for developmental control of the G1-to-S transition, but it is required for normal cell proliferation, for optimal DNA synthesis, and for efficient G2/M progression...

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..Such repression is evident in both actively proliferating cells and in cells that have withdrawn from the cell cycle...

..Thus, DP1 is absolutely required for extra-embryonic development and consequently embryonic survival, consistent with E2F/DP1 normally acting to promote growth in vivo...

..One thorny issue remains: do our current molecular models of E2F and retinoblastoma action explain all of the functions of these proteins in vivo?..

..As a result, dE2F/RBF regulation is used to link gene expression with cell cycle progression at some targets while simultaneously providing stable repression at others...

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..These results uncover an unexpected link between pRB/RBF1 and chromatin condensation, providing a mechanism by which the functional inactivation of RB family members in human tumor cells may contribute to genome instability...

..The results reveal an unexpected physical convergence between the pRB tumour-suppressor protein and E3 ligase complexes, and raise the possibility that pRB may direct APC/C to additional targets during pRB-mediated cell-cycle exit...

..Therefore, inhibition of Api5 function might offer a possible mechanism for antitumor exploitation...

..These results demonstrate the surprising finding that pRb uses the LXCXE binding cleft to control chromatin structure for the regulation of events beyond the G(1)-to-S-phase transition...

..These results demonstrate that RBF2 has a unique function in repressing E2F-regulated differentiation markers and that dE2F2 and RBF2 are required to regulate different sets of target genes in different tissues...

..These residues most likely form ionic interactions with conserved acidic amino acids on E7 since a stable pRB/E7 interaction was restored when the lysine residues on pRB and the acidic residues on E7 were interchanged...

..The implication of these results is that cells containing dE2F2 require dE2F1 to either prevent, or reverse, dE2F-mediated repression...

..Thus, by retaining RB1 and amplifying CDK8, colorectal tumour cells select conditions that collectively suppress E2F1 and enhance the activity of beta-catenin...

..In the previous period we discovered that cells homozygous mutant for both de2fl and de2f2 can proliferate. Aim 3 will use E2F- or DP-deficient cells to determine which aspects of cell cycle regulation require E2F activity. ..

..The LXCXE-binding cleft is maintained in all pRB-homologs that have been identified, suggesting that it is critical for a conserved function of pRB. ..

..Starting from the list of genes isolated in the screen we plan to identify and characterize proteins that limit E2F-dependent proliferation, and proteins that are needed for the activation of dE2F1-dependent transcription. ..

..By examining cells as they respond to different types of cell cycle arrest signals we will also discover whether pRB recruits different types of repressor complexes in different contexts. ..

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..3) identify and characterize a novel regulator E2F that is specifically upregulated in cells lacking both p1O7 and p130. ..

..Starting from the list of genes isolated in the screen we plan to identify and characterize proteins that limit E2F-dependent proliferation, and proteins that are needed for the activation of dE2F1-dependent transcription. ..