Ch.18 Gene Mutations and DNA Repair

Somatic vs Germ line

Somatic-body

Germ line-sexual

Purines

A,G

Pyrimidines

T,C

Transition

substituting a purine for a purine/pyrimidine for a pyrimidine

Transversion

Purine swap for pyrimidine

Frameshift mutations

Insertions and deletions of 1 bp that affects the aa sequence

TTG ATC CCT

In frame insertions

Multiple of 3 bp’s added so AA seq added, not changed

TTG ATC CCT

Forward mutation

wild type→mutant type

Reverse mutation

mutant type→ wild type

Missense mutation

affects amino acids, not bases

Nonsense mutation

sense codon→ nonsense codon (stop)

Silent mutation

base change, but silent bc it still makes same amino acid (can still change phenotype)

intragenic suppressor mutation

suppresses mutation of another mutation on same gene

intergenic suppressor mutation

suppresses mutation of another mutation on different gene

Factors affecting mutation rates

Frequency

Probability of detection

Probability of repair

Causes of mutations

replication errors

chemical changes

radiation

Spontaneous vs induced mutations

Spontaneous—mutation under otherwise normal conditions

Induced—Environment or chemical conditions

Tautomeric shifts

tautomers—shift in protons of bases

results in C-T or G-A mispairing

Wobble

leads to replication error—other than wild type

nonstandard base pairing

due to wobble position

A—C

Depurination

loss of purine (A,G)

Deamination

loss of aa group

Mutagen

agent that increases mutations

Base analogs

chemical substances similar to bases that may be incorporated into a DNA strand

Disguised to get in

Chemically induced mutations

Alkylating agents

Deamination

Hydroxylamine

Oxidative reaction

Intercalating Agents

Intercalating Agents

distorts the DNA double helix

Radiation

penetrates tissues and dislodges electrons from atoms

creates bubble in DNA molecule

Pyrimidine dimer

two thymine bases block replication—distorts DNA molecule

Transposable elements

sequences that can move about the genome

Makeup of transposable element

___—________—___

Flanking direct repeat (outside of transposable element)

Transposable element

Terminal inverted repeats found on ends of transposable element

Replicative transposition

new copy of DNA inserts itself in a new location

Nonreplicative transposition

old copy of DNA excises from old site and inserts itself in a new location

Retrotransposons

RNA transcribed from DNA, but transposable element copied back into DNA

Control of transposition

DNA methylates at common transposable element sites to decrease transposition

How can transposons cause mutations?

Inserting themselves into another gene

Promoting DNA arrangements

Bacterial transposition

insertion sequences on each side of transposon

Noncomposite Bacterial transposition

type of Bacterial transposition that lack insertion sequences

Eukaryotic transposition

Class I-retrotransposons-RNA

Class II-DNA

Class I

long terminal direct repeats

short flanking direct repeats

Class II

short terminal direct repeats

short flanking direct repeats

Who discovered transposable elements?

Barbara McClintock

Methods of DNA repair

Mismatch repair

Direct Repair

Base-excision repair

Nucleotide excision repair

Mismatch repair

replication errors such as mispaired bases and strand slippage

Mismatch-repair complex binds, cuts out section

Direct repair

restores correct structure of altered nucleotides

Ex. pyrimidine dimers

Base-excision

damaged bases recognized and removed (AP site)

Nucleotide-excision

Double strand of DNA has single strand damage

uses Single Stranded Binding proteins to cleave and remove damage

Double stranded break repair

Homology directed repair

Nonhomologous end joining

Homology directed repair

Double stranded repair that takes a homologous DNA template and inserts it into DNA

Nonhomologous end joining

Double stranded repair that joins ends, may result in insertions or deletions

Translession DNA polymerases

allow replication to proceed past distortions, often results in errors as a result