BS 161 CH 14

Chromosomal mutations involve large regions of one or more chromosomes.

- Large chromosomal mutations can occur and are much more damaging than small point mutations. oDuplications and deletions both affect gene dosage, which can have important effects on a cell or organism. oGene duplication (followed by the accumulation of point mutations) results in "gene families" made up of genes with related but not identical functions. This process is important in evolution.

Enzymes proofread DNA during its replication and repair damage in existing DNA.

- Mistakes during the initial pairing of template nucleotides and complementary nucleotides occur at a rate of one error per 100,000 base pairs. • DNA polymerase proofreads each new nucleotide against the template nucleotide as soon as it is added. • Mismatched nucleotides that are missed by DNA polymerase proofreading or mutations that occur after DNA synthesis is completed can often be repaired. • In mismatch repair, special enzymes fix incorrectly paired nucleotides.

Describe different types of mutations and their effects on the processes of the central dogma.

- Point mutations are changes in a single nucleotide. A nucleotide substitution is a change of one base for another. The effect of a point mutation depends on where it occurs. o If the mutation occurs in an exonofaprotein-coding gene, it can result in a change in the amino acid sequence (a missense mutation), no change in the amino acid sequence (silent mutation) or the introduction of a stop codon (nonsense mutation). - Small Insertions or Deletions in DNA add or remove one base (or a few bases). Again! Their effect depends on where on the chromosome they occur and on their size. o An insertion or deletion in a protein-coding gene can result in a"frameshift" mutation, in which all the codons downstream of the insertion or deletion are changed. - Mutations in non-coding regions of the genome or silent mutations do not affect "Phenotype (physical characteristics) but allow the accumulation of differences in "Genotype (the sequence of your DNA)"

Mutation

---> Any heritable change in the genetic material. By heritable, we mean that the mutation is stable and can be passed on through cell division. - Mutations result from mistakes in DNA replication or from unrepaired DNA damage. - Only germ-line mutations are transmitted to offspring. - In somatic cells (non-reproductive cells), mutations affect only the individual in which they occur. o Most cancers result from mutations in somatic cells. Cancer causing mutations allow the cell to escape from the normal processes that control the cell cycle (cell division).

Define "mutagen" and name two common mutagens and their effects on DNA.

DNA molecules are constantly subjected to potentially harmful chemical and physical agents. • Reactive chemicals, radioactive emissions, X-rays, ultraviolet light, and molecules in cigarette smoke can change nucleotides in ways that can affect encoded genetic information. o Mutagens increase the probability of a mutations by a factor of 100 or more. o UV light: can cause adjacent thymines to crosslink (thymine dimers) o X-rays can cause breaks in the sugar-phosphate backbone of DNA. o Bleach or hydrogen peroxide can cause the loss of a base. o Tobacco smoke can add bulky side groups to the bases (results in improper basepairing during replication).

Describe how Nucleotide excision repair works.

Many cellular systems for repairing incorrectly paired nucleotides use a mechanism that relies on the base-paired structure of DNA. o A nuclease cuts out a segment of a damaged strand, and the resulting gap is filled in with nucleotides, using the undamaged strand as a template. o One such DNA repair system is called nucleotide excision repair. • DNA repair enzymes in skin cells repair genetic damage caused by ultraviolet light. ○ Ultraviolet light can produce thymine dimers between adjacent thymine nucleotides. ○ This buckles the DNA double helix and interferes with DNA replication. • The importance of the proper functioning of the enzymes that repair damage to DNA is clear from the inherited disorder xeroderma pigmentosum. ○ Individuals with this disorder are hypersensitive to sunlight. ○ Mutations in their skin cells are left uncorrected and cause skin cancer.