Mutation and Repair of DNA

Explain mutation of DNA.

Mutation is defined as a heritable change in the DNA. It can take place on a smaller scale (e.g. a change of bases) or a larger scale (e.g. chromosomes fusing together).

Describe the processes that result in the mutation of DNA.

There are several different ways in which mutations can be acquired. Some arise from errors when the DNA is replicated. This is a very rare occurrence- DNA replication and the DNA proofreading processes are so good that the error rate is only 1 in 10^9 bases. Exposure to certain environmental factors, such as radiation, certain chemicals and infectious agents, may also cause damage to the DNA.

Describe the consequences of depurination, deamination, thymine dimer formation and double stranded breaks on DNA replication.

Depurination is the loss of a base from the DNA backbone. During replication, this base will simply be skipped.

Deamination is the loss of amine groups from bases. This can cause unnatural bases in the DNA, which may pair up with different bases during DNA replication. For example, when cytosine is deaminated, it forms uracil, which will pair up with adenine during DNA replication.

Thymine dimers can occur when DNA is exposed to UV light. A thymine dimer is when two adjacent thymine residues bind to each other rather than to their complementary bases on the other strand.

Double-stranded breaks are basically when both strands are broken. There are also single-stranded breaks in which one strand is broken. One cause is exposure to gamma or X-rays, which either produce free electrons or generate hydroxide radicals, both of which can attack the DNA backbone.

Understand how transposable DNA elements and infectious agents introduce mutations into DNA.

Transposable DNA elements and infectious agents can integrate themselves into DNA, which in turn can disrupt the function of whatever part of the DNA they happen to find themselves in. For example, if a transposable element is moved into the middle of a region coding for a gene, the function of this gene will be disrupted. Transposons essentially enter via a cut-and-paste kind of method: transposases (which are encoded by the transposons themselves) "cut" out the transposon from the original DNA and then "paste" it somewhere along the host DNA strand. Once in the new DNA strand, it can continue to replicate along with the DNA.

Explain the two mechanisms for DNA repair: MisMatch repair system and homologous recombination.

As mentioned above, DNA has several proofreading and repair mechanisms that are partially responsible for the low rate of mutations.

Mismatch repair is a relatively simple process. Firstly, mispaired bases are recognised by repair proteins. This may be due to the change in thickness of the strand at that point- as alluded to in an earlier post, two purines or two pyrimidines pairing together may result in the DNA being too thin or thick at that point. The wrong base is removed by nucleases. The correct base is then added in and the gap in the backbone is sealed with DNA ligase.

Homologous recombination is relatively complex and is used to repair double-stranded breaks in the DNA. It is called "homologous" because extensive regions of similarity are required for it to work. Often it takes place right after the DNA has replicated. The first step of homologous recombination is to remove some nucleotides from the 5' to 3' direction, leaving 3' overhangs. These overhangs can then move into a chromosome with the same sequence (as I said, it generally takes place right after DNA replication, when such chromosomes are available), where DNA polymerase can add more nucleotides to them. (The region where the overhangs "cross over" into the other chromosome is known as the Holliday junction.) When enough DNA has been synthesised, the chromosomes can be resolved by strand cutting. A similar process is also used for crossing over of chromosomes during prophase I of meiosis.