6.7: DNA Helicases and Single-strand DNA-binding Proteins
DNA unwinding enzyme helicases are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates along the lagging strand template in the 5' to 3' direction. In eukaryotes, the minichromosome maintenance (MCM) protein complex is a DNA helicase that binds and translocates along the leading strand template in the 3' to 5' direction.
Helicases as Therapeutic Targets
Being an indispensable component of the DNA replication machinery, helicase is emerging as a new target for the development of drugs against bacterial and viral infections and for cancer treatment. Cancer cells are characterized by rapid proliferation, which demands a high DNA replication rate and a corresponding increase in the production of MCM helicase. Thus, inhibition or depletion of MCM helicase by the right drugs could suppress the rapid growth of cancer cells.
Single-strand DNA-binding (SSB) Proteins – Stabilizer and Protector of Single Stranded DNA (ssDNA)
For successful DNA replication, unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. Binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes it rigid. This is believed to enhance DNA polymerase's ability to correctly select bases, thereby increasing the fidelity of DNA replication.
The ever-growing threat of drug-resistant microorganisms demands development of antibiotics with new targets. Due to their involvement in DNA replication, recombination, and repair, SSB proteins are being investigated for this purpose.