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Understanding Cancer: The Genetics of Cancer

DNA Transcription and Protein Assembly

An Overview of Genetics

DNA Replication

DNA is a molecule made of a nitrogenous base, a sugar (specifically a deoxyribose), and a pairing of several nucleotides.  DNA, the genetic blueprint of life (it passes on characteristics from a parent to an offspring), is replicated in cells through the combined efforts of several different proteins and enzymes working cooperatively.  In the replication process, the DNA's helical strands must first be unraveled; this is performed by the protein helicase.  After the strands of DNA are unraveled, single-strand binding proteins attach to the strands, stabilizing the DNA, and preventing the nucleotides from re-pairing.  An additional protein, topoisomerase, prevents the strain of unwinding the DNA from becoming too great.  At this point in the process, a copy of the DNA is not yet ready to be formed; the cells need a starter molecule called an RNA chain that is a primer for the process.  The protein primase performs this job and the cell is ready to begin producing copies of DNA strands.  DNA polymerase III, an enzyme that begins the formation of DNA, starts producing complementary copies of DNA, although only in the 5' => 3' directions.  To make up for this, DNA is replicated at several different locations simultaneously.  The starting strand of replication is the leading strand, and all other replicating strands are lagging strands, which are made up of various fragments of RNA starter chains and DNA strands. A protein called DNA polymerase I lags behind the production of DNA strands and replaces all RNA fragments with DNA strands.  The two DNA polymerases also act as a proofreading mechanism, thereby correcting errors in replication.  Finally, the enzyme DNA ligase fills any gaps in the DNA strands that are caused by the discontinuous replication.  Occasionally, DNA will require repair; in addition to DNA primase and ligase, nuclease enzymes function in this domain.  Over time, DNA strands tend to lose portions at their ends, making for rough ends.  To prevent these ragged edges from interfering with a cell's ability to replicate, and therefore reproduce, a cell has groups of specially organized nucleotide sequences called telomeres at the end of DNA strands.  Telomeres do not contain genes; instead, they act as protectors of genes.  When DNA shortening occurs, it is the telomeres that take the hit and cushion the "important" DNA.  For cells that must remain unchanged, such as germ cells, the enzyme telomerase lengthens telomeres.  Interestingly enough, unauthorized telomerase activities may well contribute to cancer, as they allow the cell to undergo cell division almost an infinite number of times without destroying the telomeres.

RNA Splicing

mRNA strands, lengths of RNA that send messages to various parts of the cell for the purpose of protein production, are manufactured within a cell's nucleus for the express purpose of coding for protein production in ribosomes (the protein factories of the cell).  The protein, RNA polymerase, is responsible for making mRNA strands; it begins the process by unwinding the cell's DNA and forming complementary copies of RNA strands.  Like DNA polymerases, RNA polymerases act only in a 5' => 3' direction; unlike DNA polymerases, however, no starter strand is required to activate RNA polymerase.  The place where RNA polymerase begins formation of the mRNA strand, also known as transcription, is called the promoter.  The DNA sequence that signals the end of transcription is called the terminator.  The area of DNA between them is the transcription unit.  The binding of RNA polymerase is initiated by transcription factors, a group of proteins.  During the creation of mRNA, the molecule that sends information to the cell's ribosomes in order to produce proteins, many sections of nonreplicative mRNA are made.  These portions are called introns.  For the most part, mRNA strands called extrons are the portions that are used to code for proteins.  Surprisingly, introns make up a larger portion of mRNA than extrons.  As a result, a protein complex known as a spliceosome, which is almost the size of a ribosome, cuts out the mRNA's introns in a process known as RNA splicing.  Mutations to one of the proteins that make up the spliceosome, SF3B1, have been associated with an increased risk of certain cancers.