Researchers have looked in detail at how phages use Z-DNA to evade the attack of host restriction enzymes.
DNA is the genetic material of life. It consists of the bases – adenine, thymine, cytosine and guanine – that follow the Watson and Crick base pairing. Researchers have found that there is a single exception to this – a virus that infects bacteria and uses its own unique base. In 1977, researchers reported that the genome of cyanophage S-2L, which infects cyanobacteria, was able to substitute adenine with diaminopurine (Z) in the genome. Diaminopurine is structurally similar to adenine but has an extra nitrogen attached to one side. This enables it to form three hydrogen bonds when base-paired with thymine. DNA that incorporates diaminopurine is also known as Z-DNA. Unlike other types of nucleobase modifications, Z is unusual in altering typical base pairing. It changes the physical, chemical and mechanical properties of double-stranded DNA.
To date, cyanophage S-2L is the only known organism that possesses the Z base in its genome. It has also been identified in carbonaceous meteorites, suggesting its role in the origins of life. However, the biosynthesis, prevalence and importance of Z genomes remains unclear.
Z-DNA in phages
In this study, published in Science, researchers explored the system that supports Z-genome synthesis. The S-2L genome contains an open reading frame encoding PurZ. This is a homologue of PurA in the purine biosynthetic pathway. A deeper look at the protein it encodes, revealed that several of the amino acids involved in catalysing chemical reactions are different. These differences affect what molecules can fit into the catalytic site. The team then found that dozens of globally widespread phages harbour such enzymes.
The researchers made some of the PurZ viral protein and incubated it with raw substrates. They found that instead of making a precursor of adenine, the protein made a precursor of diaminopurine. Another enzyme present in bacteria was then able to convert it into the mature Z-DNA base. This suggests that the virus carries everything needed to make its own Z-DNA.
By looking at the dozens of viruses that have a similar version of this gene, the researchers identified that it was present in genomes that contained a couple of additional genes. For example, one gene appeared to be involved in ensuring enough chemical precursors were present. The team found over 60 viral genomes that contained a combination of these genes – emphasising that Z-DNA is more regular in viral life than previously thought.
The Z genome enables the phage to avoid being cut by bacterial restriction enzymes, which researchers could potentially harness in a diverse range of applications.
Image credit: By Science Photo Library – canva