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Figure 5 Homologous recombination repair of DNA DSB. (a) Damaged and undamaged homologs pair up; (b) damaged sections are removed by nucleases; (c) damaged and undamaged homologs cross over, polymerases use undamaged homolog to synthesize new DNA in damaged homolog; (d) DNA is cut at crossovers and ligated.

correct synthesis of new DNA, this may result in loss or changes in DNA sequence.


Types of Mutations

DNA damage can result in a variety of mutations, including point mutations, frameshift mutations, and chromosomal mutations. Point mutations include changes in DNA sequence due to substitution of one base for another during DNA replication. For example, the DNA sequence AATTCGCATTG could be replicated as AACTCGCCTTG. Changes in DNA sequence may or may not result in changes in amino acid sequence when the mutated DNA is used to code for protein. When DNA is translated into proteins, every three nucleotide bases (a 'codon') code for one amino acid. However, many amino acids are coded for by more than one codon. Thus, if a mutation occurs such that the mutated sequence codes for the same amino acid sequence as the old sequence, this is called a silent mutation. In evolutionary terms, this is also referred to as a neutral mutation. Silent (or neutral) mutations may also occur if there is a change in the amino acid sequence, but this does not alter the structure of the protein. However, if a point mutation results in a change in the structure or function of the protein, a nonfunctional, dysfunctional protein or a protein with impaired function could result. This is called a missense mutation. In addition, in a coding sequence of a gene, there are start codons and stop codons - locations that determine where the translation of the protein will begin and end on the mRNA molecule. If a mutation results in a premature stop codon, this will result in a truncated protein. This is known as a nonsense mutation, because the protein coded for by the mutated DNA is entirely nonfunctional. Another change in DNA sequence occurs if nucleotides are added or subtracted from the coding region. This is called a frameshift mutation, because it changes the reading frame and leads to a complete change in the amino acid sequence coded by the DNA.

Chromosomal mutations (also known as cytogenetic mutations) are changes in the structure or number of chromosomes. Chromosomal mutations are alternatively called chromosomal aberrations, chromosomal rearrangements, cytogenetic effects, cytogenetic aberrations, or clastogenic effects. The process of producing such effects is referred to as clastogenesis. Chromosomes can be visualized when they condense during mitosis or meiosis, and can be stained with various dyes. Because some regions stain darker than others, this produces a banding pattern when the chromosome is observed under a microscope. An unreplicated chromosome with a representative banding pattern is schematically illustrated in Figure 6a. The circle at the center represents the centromere: the place where the mitotic spindle attaches during cell division. The numbers refer to various positions on the undamaged chromosome. A DSB may lead to a break in the chromosome, as illustrated in Figure 6b.

If this break is unrepaired, it may lead to loss of a portion of the chromosome, called a deletion. If a piece of chromosome is deleted from the end, as illustrated in Figure 6c, this is called a terminal deletion. If there are

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