(1). A major response is to halt cell cycle progression with corresponding activation of genes needed for DNA repair. A second kind of response is apoptosis (2). Genotoxic stresses activate many cellular kinases that phosphorylate various serine and threonine residues in p53, as well as enzymes that cause lysine acetylations (3). Presently, at least 12 serine/threonines and 2 lysines are known to be modified in p53 and there may be more modification sites. This signaling system and the code of post-translational modification are still incompletely understood (1). An understanding of the structural basis of such signal integration and transduction remains a distant dream.p53 is a multidomain protein. The N-terminal domain 1-73 is responsible for transactivation function and binding of such proteins as Mdm2/Hdm2, which down-regulate the levels of p53 (4). The N-terminal domain of p53 is emerging as one of the most important regions in p53 function. One of the major pathways of transactivation is through interaction with p300/ CBP 1 and recruitment of this protein to the required promoter region. p300/CBP has well known histone acetyltransferase activity, which results in histone acetylation and remodeling of the chromosome in that region leading to enhanced transcription (5). Clearly, interactions of the N-terminal domain of p53 with Mdm2 and p300/CBP and possibly with other regulatory proteins are of crucial importance in understanding the various roles played by p53 as the guardian of the genome.Although crystal or NMR structures of other domains have been reported (6, 7), very little is known about the structure of this important domain. Only very recently, an NMR study of this domain has shown this to be disordered, although the authors concluded that secondary structural elements are present (8). It now appears that there are at least eight phosphorylation sites within the N-terminal subdomain: serines 6, 9, 15, 20, 33, 37, and 46 and threonine 18 (1). Functions of several of these phosphorylations are not clear. However, it appears that the Ser-15 phosphorylation plays a crucial role in the transactivation process (9 -11). Phosphorylation of Ser-15 occurs very soon after initial stressing of the cells (12). Among * This work was supported in part by the Nissan Science Foundation and a grant-in-aid for scientific research (to K. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.§ 1 The abbreviations used are: CBP, cAMP-responsive element-binding protein-binding protein; Pep53, peptide corresponding to residues 17-28 of human p53; Bpep53, same peptide as Pep53 except five ␣-aminoisobutyric acid residues incorporated in designated positions; Aib, ␣-aminoisobutyric acid; Ser15P, p53-(1-39) domain phosphorylated at serine 15; Thr18P, p53-(1-39) domain phosphorylated at threonine 18; Ser20P, p53-(1-39) domain phosphorylated at serine ...

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An unusual lilamentous bacteriophage, VSK, containing single-stranded, circular DNA as its genome was isolated from Vibuio cholerae 0139 strains PO7 and B04. Unlike other single-stranded DNA phages, VSK can integrate its genome into the chromosome of the host and enter into a lysogenic state. The double-stranded replicative form (RF) of the single-stranded phage DNA was isolated. A restriction map of the VSK RF DNA was constructed using HaeII, AvnII, ClaI and XbaI. By Southern blot analysis of the chromosomal DNA of the lysogen using labeled phage DNA as probe, the attachment site (attP) on the viral genome was also identified.

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