lecture 2 Flashcards
define mutation
change in DNA sequence/rearrangment of genetic material
what is the difference in terms of impact, between a heritable genetic mutation and an acquired genetic mutation?
heritable (germline) mutation can drive evolution
acquired (somatic) mutation can cause disease (e.g. cancer)
what are the sources of genetic mutations?
misrepair of DNA damage spontaneous events (e.g. DNA replication errors, transposable elements)
how do double stranded DNA breaks occur?
if two single stranded breaks occur close together
can be caused by ionising radiation
why are double stranded DNA breaks a problem?
- disrupt molecular continuity
- difficult to fix
- cytotoxic + genotoxic
how can double stranded DNA breaks lead to insertions/deletions?
when DNA ends are ligated back together by the error-prone end-joining pathway
what are alkylating agents?
mutagens which add alkyl groups to bases, causing base substitution
what are intercalating agents?
mutagens which add/delete single nucleotides at replication, inducing frameshift
what are the opportunities for mutagenesis in DNA replication?
slippage in repetitive sequences- causes insertion/deletion
replication fork slippage- results in extra/missing nucleotide
-nucleotide misincorporation
what problem does nucleotide misincorporation result in?
defects in exonuclease, which has 3’-5’ proofreading ability
what is a point mutation?
changes to a single nucleotide pair of a gene
what are the implications of a frameshift mutation?
all nucleotides downstream of the deletion or insertion will be improperly grouped into codons
how does UV light exert its mutagenic effect?
causes disruptive thymine dimers
what are tautomers and how do they cause mutation?
- the alternate form a base can take
- keto form is responsible for normal pairing
- enol form can cause mispairing of bases
what effect does replication fork slippage have?
an extra or missing nucleotide
