We have determined the DNA sequence of the long unique region (UL) in the genome of herpes simplex virus type 1 (HSV-1) strain 17. The UL sequence contained 107943 residues and had a base composition of 66-9~ G+C. Together with our previous work, this completes the sequence of HSV-1 DNA, giving a total genome length of 152260 residues of base composition 68.3~ G+C. Genes in the UL region were located by the use of published mapping analyses, transcript structures and sequence data, and by examination of DNA sequence characteristics. Fifty-six genes were identified, accounting for most of the sequence. Some 28 of these are at present of unknown function. The gene layout for UL was found to be very similar to that for the corresponding part of the genome of varicella-zoster virus, the only other completely sequenced alphaherpesvirus, and the amino acid sequences of equivalent proteins showed a range of similarities. In the whole genome of HSV-1 we now recognize 72 genes which encode 70 distinct proteins. INTRODUCTION In the last decade, the study of animal viruses has been revolutionized by the application of nucleic acid sequencing techniques to viral genomes. Many smaller virus genomes have been completely sequenced, and the sequences interpreted to give high resolution views of the genetic organization and the nature of the encoded proteins, while comparisons of sequences have enhanced our understanding of relationships between viruses. For larger virus genomes, total determination of nucleotide sequence remains a formidable undertaking, and only two complete sequences of virus genomes larger than 105 residues have been published. These are for the gammaherpesvirus Epstein-Barr virus (EBV) of 172282 residues (Baer et al., 1984) and the alphaherpesvirus varicella-zoster virus (VZV) of 124884 residues (Davison & Scott, 1986a). In this paper we report a third complete herpesvirus genome sequence, that of herpes simplex virus type 1 (HSV-1), which comprises 152260 residues. The molecular biology and genetics of HSV types 1 and 2 have been widely investigated such that overall they are the most extensively characterized of the family Herpesviridae. A decade ago, studies on the structure of HSV DNA showed it to be a linear molecule which could be viewed as consisting of two covalently linked segments, designated long (L) and short (S). Each segment contains a unique sequence flanked by a pair of inverted repeat sequences, as shown in Fig. 1. The long repeat (RL) and short repeat (Rs) sequences are distinct. The molecule also

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Oncogenic forms of the non-receptor tyrosine kinase Src alter cell structure, in particular the actin cytoskeleton and the adhesion networks that control cell migration, and also transmit signals that regulate proliferation and cell survival. Recent work indicates that they do so by influencing the RhoA-ROCK pathway that controls contractile actin filament assembly, the STAT family of transcription factors needed for transformation, and the Cbl ubiquitin ligase that controls Src protein levels. These studies also shed light on the role of focal adhesion kinase (FAK) downstream of v-Src and other signalling pathways in controlling migration, invasion and survival of transformed cells. Src directly phosphorylates integrins and can also modulate R-Ras activity. Moreover, it stimulates the E-cadherin regulator Hakai, interacts with and phosphorylates the novel podosome-linked adaptor protein Fish, and progressively phosphorylates the gap junction component connexion 43. A recurring theme is the identification of novel and important Src substrates that mediate key biological events associated with transformation.

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