The appreciation that the macromolecule deoxyribonucleic acid (DNA) encodes for heritable information heralded the modern era of molecular studies in medicine. The quest to understand how genetic information can be perpetuated can be traced back to Gregor Mendel, whose work in the 19th century indicated that genes are the discrete elements that govern specific heritable traits. The work of Frederick Griffith, Oswald Avery, and Martha Chase demonstrated that genes were composed of DNA. The proposal by James Watson and Francis Crick that DNA was a double-helix model was a monumental discovery that provided an immediate explanation for transmission of heritable information. Because DNA is composed of two strands that were mirror images of each other, each strand can serve as a template for the synthesis of daughter strands to perpetuate information from parent to offspring (Fig. 6–1).
The central dogma. DNA resides in the nucleus. Replication of DNA is required for the perpetuation of genetic information. Through the process of transcription, information in DNA is transferred to an mRNA. The RNA translocates from the nucleus to the cytoplasm where it is translated into protein.
Although these observations provided the foundation for the modern molecular era, they did not address how the information coded in genes leads to proteins that govern cellular activities. In this regard, seminal studies by George Beadle and Edward Tatum led to the appreciation that genes could result in polypeptides (one gene–one enzyme hypothesis). The final link came from the work of Francois Jacob, Jacques Monod, Sidney Brenner, and Matthew Meselson, whose work identified an intermediate between gene and protein termed messenger ribonucleic acid (mRNA). These findings were critical in establishing the paradigm (see Fig. 6–1) that information in DNA is transferred to mRNA (termed transcription) and ultimately to proteins (termed translation).
The transfer of information from DNA to RNA is a complex multistep process that involves unwinding of specific regions of compacted DNA, transfer of genetic information from DNA to a nascent mRNA single strand, and then transport of the mRNA to the cytoplasm for protein production. The use of mRNA as an intermediate is important for several reasons. First, it allows the cell to separate information storage from information utilization. Information remains stored in the large and stationary nuclear DNA molecule but is transmitted to the cytoplasm to direct protein expression by the mobile RNA molecule. Second, because one DNA molecule can produce many mRNA molecules, the signal can be greatly amplified to enhance synthetic output. In the following sections, we discuss in detail the steps through which information from DNA is transferred to RNA and ultimately to protein synthesis.
DNA is comprised of two strands of polydeoxyribonucleotides that twist around each other to form a right-sided spiral coil. The basic building block of DNA is ...