Lecture 4 Flashcards
What are some ways to categorise mutations?
point mutations are muations ina single point (most often single base pair) within a genome, mutations within genes can be substitution mutations or indels (insertion/deletion of base-pairs), mtations can also arise through deletion or large scale rearrangement of chromosomal DNA or insertion of mobile genetic elements.
What are spontaneous mutations? How do they typically occur?
most mutations occur spontaneously (no evident external cause), this requires DNA synthesis which can involve mistakes by DNA polymerase toptomerisation of bases, a base transiently flips into a different isomer with different pairing properties (forming a mismatch, two bases which don’t properly match, this can lead to the base which was previously in the isomeric form could be removed, leading to a new DNA sequence).
What is proofreading in regards to mutations?
DNA polymerase “checks” each new base-pair, if it has made a mistake it backs up, removes the incorrect base (99%) effective) and DNA synthesis resumes, (it checks as it goes). This is important to reduce spontaneous mutation in bacteria and other organisms (lack of this leads to premature aging of mice).
What does the mismatch repair system rely on?
The mismatch repair system can detect non-matched “pairs” of bases in DNA molecules, which of the bases is wrong and removes the wrong base. It can distinguish the original and new strands of the DNA, this can be done because DNA is modified by a process known as methyllation, this is a chemical modification of adenine.
How does the mismatch repair system work?
The mismatch repair system works on DNA templates undergoing duplication, MutS recognizes the mismatched pair and signals this to other enzymes, then MutH and MutL recognize the methylated parent strand and nicks the daughter strand, the new strand is then excised and replaced between the nick and the mismatched pair.
How do frameshift mutations occur?
Frameshift mutations are insertions or deletions of one or more base pairs, these are though to arise through an error during DNA replication where DNA “slippage” results in loss or incorporation of a new base pair into the DNA. The slippage is loss of a base pair because one base slips out of the linear sequence. This slippage can occur either on the new strand or the template strand (new strand slippage (+ 1addition) or template strand slippage (- 1deletion) respectively. The mismatch repair system can also recognise this by spotting the kink.
What is the overall accuracy of DNA duplication?
Inherent accuracy of DNA polymerase is 1 in 10^5, proofreading corrects 99%, mismatch corrects 99% of remainder, overall this means spontaneous mistakes occur in about 1 per 10^9 basepairs.
