8 Virus-encoded DNA Topoisomerases

Abstract

I. INTRODUCTION
The ubiquity of DNA topoisomerases is now well established. These enzymes participate in many vital aspects of DNA metabolism including replication, transcription, recombination, and chromosomal segregation. In virus-infected prokaryotic and eukaryotic systems, the host DNA topoisomerases are usually recruited to perform the functions needed for virus growth and development. Two relatively large and complex double-stranded DNA (dsDNA) viruses, one in prokaryotes and one in eukaryotes, are known to encode their own topoisomerases that are required for viral growth and development. Bacteriophage T4 and its relatives encode a type-II ATP-dependent DNA topoisomerase, whereas vaccinia, a poxvirus, encodes a type-I enzyme. These two viral enzymes have properties distinct from the host enzymes. Their subunit structure and activity, the organization of their coding sequence, and their possible role in virus development are the subject of this chapter.

II. T4 DNA TOPOISOMERASE
A. General Description of T4 DNA Metabolism
Bacteriophage T4 is a large lytic virus of Escherichia coli. Its genome is 166-kb pairs in length. The viral DNA is terminally repetitious with 3% redundancy. The genome is circularly permuted so that in different molecules any given gene lies at different distances from the end. Hence, the virus has a circular genetic map although the genome is a linear duplex DNA molecule. The viral DNA is modified with glucosylated hydroxymethylated cytosine in place of cytosine. These modifications protect the viral DNA from some host restriction endonucleases and may also provide an added avenue of control for the virus. T4 development follows a...