Lesson 21: Mutation II and DNA repair

What conditions do spontaneous mutations arise from and what are the two types of spontaneous mutations

Spontanous mutations arise under normal conditions in the cell

Replication errors: DNA pol puts the wrong base

Chemical changes: Chemical reactions (that are spontanous) and that changes the chemical structure of DNA which affects base pairing 

Where do induced mutations come from

Exposure to chemical or radiation that can modify the DNA

True or false: MOst mutations are repaired prior instrad of being passed down to the next generation

Ture. Mutations happen all the time and get repaired through various mechanisms in the cell

Spontaneous replication errors: what is a tautomeric shift, how does it happen, what can the tautomers do?

Tautomeric shift: THe shift converts bases to a slightly differnt chemistry and rare forms of bases (a tautomer of the base) can then base pair with a base it doesn’t usually pair with

Protons shift in position, changing the chemistry of the base

A tautemore of cytosine can base pair with a normal form of adenine

a tautomere of guanine can base pair with a common form of thymine

Spontaneous replication errors: how does base mispairing work

1. DNA strans seperate for replication

2. Thymine on the original template strand base pair with guanine through wobble leading to an incorporated error

3. At the next round of mutation, the guanine nucleotide pairs with cytosine, leading to a transition mutation

Give two differernt examples of base mispairing 

1. thymine guanine wobbe (normal base pairs)

2. Cytosine - adenine protinated wobble

Spontaenous replication errors - insertions and deletions. How does strand slippage work?

Strand slippage: One of the strands, either newly synthesized or parent strand sliped in relation to other. Think about a series of As on newly synthesized strand and stretch of Ts on template strand.

Newly synthesized strand: 

If newly synthesied strand loops out, resulting in the addtion of one nucleotide on the new strand 

If template strand slips out, leads ti imission of one nucleotide on the new strand 

Spontaenous replication errors - insertions and deletions explain unequal crossing over

Typically there is alignment in two chromosomes when crossing over occurs. If homologous chromosomes missalign (possibly because of repeats of certain nucleotide stretches) you get unequal recombination. So one chromosome picks up extra DNA sequences and the ohter loses DNA sequences 

Spontaneous chemical changed: explain how depurination works

Depurination: Either A or G (just the base, npt the sugar phosphate backbone) us cleaved off from the one prime carbon

Apurinic site: base is missing

1. in repilcation the apurinic site cannot provide a template for a complimentary base one newly synthesized strand. THe parent strand without the apurinic site is not affected. 

2. A nuceotide with the incorrect base (most ofen a) is incorperatied into the newly synthesied strand 

3. At the next around of replcation, this incorrectly incorperated base will be used as a template 

4. leading to a permanent mutation 

5. following the template strand with the apurinic site, the process starts again 

Spontaneous chemical changed- what is deamination

Demination means the removal of an amine group

In Deamination of a normal cytosine, deamination turns the cytosine into Uracil. So transition from CG pair to T-A pair after replication. Usually corrected by enzymes that remove uracil from DNA 

In deamination of modified cytosine, it turns into a thymine. Transition from a C-G pair to a T-A paur after replication. THis is frequent in mammals 

Induced mutations: what is a base analog

Base analog: chemicals that can act like a base, can be incorporated into DNA, and can act like a base

5-Bromouracil looks like thymine and it can base pair to adenine (normal pairing) but it can also base pair to guanine (mispairing) causing mutations

Induced mutations - describe base modification

Base modification is the chemical modification of bases within DNA that MAY result in mispairing. Some chemicals can also be used as cancer treatments

Give an example of base incorporation and replication error

1. in replication, 5 bromouracil may become incorporated into DNA in place of a thymine, producign in corporation erorr. 

2. during replication, the strand with the 5-bromouracil may mispair with guanine. 

3. In the next replication, rhe guanine pairs with cytosine, leaing to a permanent mutation 

4. If the 5-bromouracil pairs with adenine, then no replication errors in this round of repication 

Iduced mutations: what are oxidizers? What is their result? 

Oxidizers are a type of reaction oxygen species that have unpaired electrons. Sometimes they stal electron from biological molecule resulting in base mispairing. Typically causes a transversion 

Induced mutations - what is an intercalting agent.

Molecules that fits into DNA in the same shape as a base pair. In distorsts the DNA leading to indels. DNA pol is confused becuase it doesn’t know what base to put. Examples are proflavin and arcidine orange.