DNA Mutation and Repair Flashcards
wild type sequence
most common (normal) seq; all changes in DNA base seq are referred to as mutations
mutations
helpful/neutral/detrimental, necessary for evolution, one mechanism whereby organisms acquire new characteristics
reverse mutation (reversion)
replaces original (forward) mutation & restores the wild type genotype and phenotype
suppressor muation
at another site but it compensates for the mutation & restore the wild type phenotype; can hide or suppress the effects of other mutations; ind is double mutant w normal phenotype
intragenic
w/i the same gene’s coding seq
intergenic
in second gene’s coding seq
germline mutations
present in either (or both) the sperm or the egg that made the ind therefore present in every cell the ind has
somatic mutations
arise after fertilization during cell replication/division/differentiation/migration therefore only present in a subset of the inds cells; arise in S phase gets passed down to 1/4th of the descendants of the original cell; occurred after fertilization and only existed in subset of parent’s cells
conditional mutation
only cause consequences under certain conditions
deletions & duplications
rand from single nucleotides to pieces of chromosome that are large enough to include many genes in them
inversion & translocations
rearrange large pieces of chromosomes
numerical abnormalities
entire chromosomes can be added or deleted
point mutation
substitution, deletion, or addition of single nucleotide
transition
purine-purine substitution or pyrimidine-pyrimidine substitution
transversion
purine-pyrimidine substitution or vise versa
missense mutation
single nucleotide substitution causes one amino acid to replace another
nonsense mutation
single nucleotide substitution creates STOP codon at site of mutation and truncates protein
silent muations
do not change organism’s phenotype
synonymous mutation
doesn’t change AA content of protein; may change splicing of mRNA
neutral mutation
changes AA content of protein but has no functional consequences
genetic code is degenerate
partially redundant
in-frame deletion or insertion
insertion/deletion involving multiple of 3 so it doesn’t shift the reading frame - AA seq will be normal before and after mutation
frame shift muation
insertion/deletion doesn’t involve multiple of 3 bases - reading frame of ribosome gets shifted; all AA after are abnormal
coding sequence mutation
change activity of each molecule of the protein
mutation in promoter & other regulatory seqs
affect rate at which gene makes its protein i.e. # of protein molecules in the body
trinucleotide repeats
3 bases get repeated w diff people having diff # of repeated units in string; found in coding regions & regulatory sequences; can expand during meiosis; larger repeated string gets = more it disrupts gene function; expansions are most common but sometimes repeat can contract; expand vs contract depends on parent of origin - more likely to contract during spermatogenesis than oogenesis; can cause strand slippage
fragile X syndrome
due to expanding CGG repeat in X chromosome (Xq28) of FMR1 gene which gets methylated - silencing the gene; FraX trinucleotide repeat can also contract during meiosis - more likely during spermatogenesis, asymptomatic males carrier pass repeat to daughters who may not be affected but will pass down to children which may be big enough to affect them
common fragile sites
all over the genome in everyone’s chromosomes - not associated w disease
rare fragile sites
associated w diseases ex: Fragile X syndrome - fragile site depicted here
genetic anticipation
when repeat expands through meiosis subsequent generations are affected earlier and more severely than previous generation
transposable elements (aka transposons)
move from one place to another w/i same cell’s DNA; “cut and paste” and leave or make copy of themselves and “copy and paste” themselves into another location; 45% of human genome comes from transposons; generate direct flanking repeats when they insert; can disrupt genes if inserted in gene’s regulatory seq but can jump back out & restore gene function
inverted repeats
help transposable elements break out of their places
transposase
enzyme that makes staggered cut in DNA; creates short single stranded overhangs that are complementary to each other; transposon inserts between ends of the cut; enables transpositions
inverted terminal repeat
part of transposon
direct flanking repeat
not part of the transposon - it is created as result of transposition process
retrotransposons
use reverse transcription
transposable element as activator
if it has seq capable of acting as promoter
transposable element & chromosome rearrangements
can disrupt activity of genes
cell methylation
methylates DNA in region of transposon which inhibits production of transposase
interfering RNAs
used by cell to interrupt transposase production
spontaneous mutations
errors during DNA replication; hydrolytic & other reactions can cause base change sin DNA after replicaiton
induced mutations
environmental agents such as UV light or radon; chem exposures; metabolic by products such as superoxide ion O2-
mutagens
agents that induce mutations
wobble/non Watson-Crick basepairing
ability to pair w atypical base bc of shifts in arrangement of hydrogen bonds; leads to replication errors
depurination
hydrolysis removes purine ring from adenine and guanines = results in mutation if not corrected quickly
deamination
converts between pyrimidines by hydrolysis of NH2 group
chemical mutagens
change # of H bonds the base makes
5-Bromouracil
replaces A thymine but bonds w A guanine
reactive oxygen species
oxidize guanine to 8-oxoguanine which pairs w/ A rather than C as G should; created by normal metabolism
intercalating agents
insert themselves btwn nucleotides; inc distance btwn neighboring basepairs confusing DNA polymerase & causing insertion & deletions in DNA (ex: acridine orange, ethidium bromide)
UV and ionizing radiation
break DNA strands; cause cells to form highly reactive free radicals = cause breaks in DNA = attempt to fix may result in mutations
pyrimidine dimers
caused by sun’s UV rays; bonds form between neighboring Cs or Ts in same DNA strand preventing DNA rep; eukaryotes have special DNA polymerase eta that puts AA across pyrimidine dimer and restores DNA
mismatch repair mechanism
repairs: replication errors, including mispaired bases and strand slippage
direct repair mechanism
repairs: pyrimidine dimers, other specific types of alterations
base excision repair mechanism
repairs: abnormal bases modified bases and pyrimidine dimers
nucleotide excision repair mechanism
repairs: DNA damage that distorts that double helix, including abnormal bases, modified bases, and pyrimidine dimers
direct repair
repaired directly by chemical reactions that restore the original base w/o removing anything ex: pyrimidine dimers
photolyase
uses light E to break bonds in pyrimidine dimers which enables bases to make their proper bonds w their complementary bases again; direct repair
06-methylguanine DNA methyltransferase
removes the methyl group if guanine gets methylated; direct repair
base mismatches
repairs by base excision; mismatched bases forms bubbles in DNA double helix which are recognized by repair systems
singe nucleotide damage (ex: deaminations)
repaired by base excision
DNA polymerase beta
fills gap from base excision in eukaryotes; has no proofreading ability; 10 new mutations uncorrected per day: sometimes error leaves DNA ligase unable to seal gap; AP endonuclease comes in
AP endonuclease
returns and excises nucleotide allowing DNA polymerase beta another chance to put the right nucleotide in
nucleotide excision repair
- recognize problem 2. remove bad nucleotide(s) 3. replace w proper nucleotide(s) 4. seal w DNA ligase
methylation
differentiates old DNA strand from new one
DNA damage bypass
DNA polymerase fills in 2nd gap created by excision; newly synthesized strand is available as template
non homologous end joining
repair double stranded breaks; ends join back together results in deletion in the chromosome
homology-direct repair (HDR)
repairs double stranded breaks; two types; homologous chromosome used as template to fill gap on one of the broken strands
non crossover synthesis dependent strand annealing (SDSA)
repairs double stranded breaks; gap in other strand is filled using newly repairs strand as template
double strand break repair (DSBR)
gap in other strand is filled using other strand of homologous chromosome as template
