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Cmmb 411 > Topic 6 > Flashcards

Topic 6 Flashcards

1
Q

What is dna damage and how can it occur

A

Any modification of dna that changes its coding properties or normal function in transcription or translation

Can happen spontaneously, induced by exposure to environmental factors like chemicals or radiation, or during replication

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2
Q

What can dna damage lead to

Are most mutations harmful

A

Mutations and genetic instability

Yes

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3
Q

What can cause changes in genetic material

A

Gene mutation (can be spontaneous or induced by mutagens)

Recombination (causing chromosomal rearrangements)

Transposable elements

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4
Q

Give an example of how recombination can change genetic material

A

If the chromosomes aren’t aligned properly during recombination

In one strand a deletion of a fragment can happen and a duplication in the other

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5
Q

What can cause gene mutations

A

Replication errors

Chemical modifications

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6
Q

What are the mutations that are caused by replication errors

What is the result of replication errors

A

Point mutations

Frameshift mutations

Mismatching, deletion, insertion, causing the reading frame to be same or diff

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7
Q

What are point mutations

A

A change in a single nucleotide

Can cause missense (change in nucleotide made diff amino acid) or nonsense mutations (premature stop codon

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8
Q

What are frameshift mutations

A

The slippage of the dna pol on the template causes a deletion in the new strand

Slippage on the new strand causes an addition in the new strand

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9
Q

Guanine and adenine structure and numbering

A

Both two rings

Guanine has c=o at c6

Adenine has c-NH2 at c6

In the five c ring numbers 7,8,9

In the 6 c ring the c 6 then go clockwise backward

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10
Q

Cytosine, thymine, uracil structure and numbering

A

Single ring for all

Cytosine has c-NH2 on c 4

Thymine has c=o on c 4 and methyl on c 5

Uracil same and thymine but no methyl on c 5

Number from 1 opposite to c 4 going clockwise

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11
Q

Which atom of purine and pyrimidines form bind with the sugar

A

Purine: N9

Pyrimidine: N1

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12
Q

What is a tautomeric shift

A

The dominant keto (c=o) and amino (c-nh2)

Turn to enol (c-oh) and imino (c-nh

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13
Q

Which nucleotides can have enol forms

Which can have imino

A

Guanine thymine and uracil

Adenine cytosine

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14
Q

What can enol form of thymine base pair with

Say how it changes

A

Keto guanine

T:A then T:G

after replication C:G

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15
Q

What can enol form of guanine base pair with

Say how it changes

A

Keto thymine

G:C to G:T

After replication A:T

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16
Q

What can imino form of adenine base pair with

Say how it changes

A

Amino form of cytosine

A:T to A:C

After replication G:C

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17
Q

What can imino form of cytosine base pair with

Say how it changes

A

The amino form of adenine

C:G to C:A

After replication T:A

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18
Q

What is the result of anomalous base pairing due to tautomeric shifts

A

Base pair transitions or transversions

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19
Q

What is a transition mutation

Transversion

A

Purine pyrimidines to purine pyrimidines (ex. G:C turns to A:T)

Purine pyrimidines to pyrimidines purine (ex. G:C turns to C:G)

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20
Q

Point mutations can be categorized into

A

Translation or transversion mitations

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21
Q

What are the two steps that point mutations occur in

At what pint is it actually a mutation

A
  1. Incorrect nucleotide is inserted during replication
  2. The mismatched base is not repaired and gets replicated

In step 1 it’s just a lesion/mismatch

In step 2 it’s a mutation

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22
Q

What is the teg-1 gene

A

A gene that when mitated causes tumour enhancement and over proliferation of mitotic cells

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23
Q

What is the mutation in teg-1 (oz230)

What is the mitation called

A

The AAG changed to UAG at codon 53 (position 257) , this causes a premature stop codon

Since UAG, called amber

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24
Q

What is the mutation in teg-1 (oz189)

What is the mitation called

A

UGG to UGA at codon 142

UGA means opal

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25
Q

What is the UAA stop codon labeled as

A

Ochre

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26
Q

What does K53X means

A

Lysine

53rd codon

X means a stop codon

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27
Q

If I have codon 53 how many nucleotides it this

But in reality it’s listed as higher (257) why?

A

153 in the processed sequence

This accounts for the fact that there are introns in the genomic sequence (unprocessed sequence)

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28
Q

What are indels and how are they caused

A

Insertions or deletions

Caused by bad recombination of dna or dna pol slippage during replication

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29
Q

What is a reading frame

What changes the reading frame

A

A contiguous non overlapping 3 nucleotide codon in DNA or RNA (has no introns)

Framshift mutations

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30
Q

What happens if an indel mutation affects a multiple of 3 base pairs

A

The reading frame of the gene is unchanged since since either only one amino acid is gone or added

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31
Q

What are trinucleotide repeat/expansion disorders

Give an example

A

When expansion of repeats of CAG CGG GAA CTG cause hereditary disorders even though no frameshift happens

Ex. CAG expansion in the gene encoding Huntington causes the Huntington chorea disorder

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32
Q

What is fragile X syndrome

Who does it affect more

What gene is it in

What is the normal number of repeat , number that makes you a carrier and the disease number

A

The most common form of mental retardation and Affects men more than women

Expansion of CGG repeats in the FMR1 gene (fragile x mental retardation)

Normal is 6-54

Carrier is 55-200

Disease is 200-1000

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33
Q

What is bad about fragile X syndrome

A

The fact that the CGG repeats get more and more expanded across generations means the offspring get worse and worse symptoms

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34
Q

How can the trinucleotide repeat disease get diagnosed using PCR

A

They can measure the number of repeats by the amount of BP in the PCr product

If 300 nucleotides there are 100 repeats

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35
Q

In chemical damage of dna what can cause this

A

Hydrolytic reaction with water to damage the nucleotides and phosphodiester backbone

Electrophillic attack of the DNA backbone by alkylating agents

Reaction with oxygen species like hydrogen peroxide, hydroxyl radicals

Alteration of the dna structure by irradiation from sunlight, x ray or uv

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36
Q

All in all, chemical damage to dna can happen why

A

Dietary and environmental stressors

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37
Q

In hydrolytic damage of nucleotides what is there

A

Deamination

Depurination

Depyrimidination

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38
Q

What is deamination

A

Removal of a amine group on a nucleotide

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39
Q

What gets Deaminated and what does it turn into

A

CAG

Cytosine turns to uracil

Adenine to hypoxanthine

Guanine to Xanthine

5-me-cytosine to thymine

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40
Q

After Deamination , what can xanthine and hypoxanthine pair with

What does this mean

A

Cytosine

When guanine gets deaminated to xanthine there isn’t a problem because it’s still pairing with C

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41
Q

What does uracil pair with

A

Adenine

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42
Q

When changing from A G to hypoxanthine or xanthine what changes

A

The amine becomes c=o and the n gets an h

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43
Q

Where would we see 5 methyl cytosine

A

In CpG islands

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44
Q

In hydrolytic damage How does depurination and de pyrimidation happen

A

The hydrolytic reaction cleaves the glycosidic bond between the base and the backbone sugar

This makes an abasic site (Ap site)

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45
Q

How often does dpurination occur

A

Under physiological condition 5000 bases per cell per day

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46
Q

What can be the result of the ap site

A

The backbone is unstable

When is becomes unstable the sugar is in the open form and vulnerable to a nucleophile attack

This leads to cleavage/breakage of the backbone

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47
Q

What causes oxidative damage of nucleotides

Give examples

A

Cellular metabolism like respiration can make reactive oxygen species (ROS)

The ROS are OH radicals, O2 radicals, and h2o2

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48
Q

What can ROS do to which nucleotides

What does each turn into

A

Oxidize T and G

T turns to thymine glycol

G turns to 8-oxoguanine

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49
Q

What does thymine glycol and 8-oxo-guanine look like

A

Thymine glycol has two OH

8-oxoguanine has two c=o

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50
Q

What do thymine glycol and 8-oxoguanine result in

A

Thymine glycol is bulky due to the two OH so it stall the dna pol during replication

8-oxoguanine pairs with adenine

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51
Q

What causes alkylating damage of nucleotides

A

Alkylation’s agents (ch3-) from cigar smoke and environmental pollution

The agent acts as a nucleophile

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52
Q

What are the highly reactive sites of the nucleotides that can get alkylated

A

N3 of A

O6 of G

N7 of G

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53
Q

What’s a special case of methylation of a nucleotide

A

S- adenosylmethionind (SAM) , a methyl donor to adenine can turn adenine

Into N6 methyladenine (m6A)

This makes the modified adenine behave like rna

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54
Q

What causes Deamination

A

In food preservatives , the sodium nitrate naNO3 and bisulfite HSO3- and nitrous acid (HNO2)

cause Deamination

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55
Q

How can bisulfite help in bisulfite sequencing in studying epigenetics

A

The unmethylated cytosine gets deaminated into uracil

So after replication it goes from C:G to T:A

But methylated stays the same

This is how you can see which were methylated

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56
Q

What is special about guanine in terms of the modifications it can have

A

It’s can have alkylation Deamination and oxidation all at the same time on that one base

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57
Q

What is the cause of uv induced damage on dna

What is the most common result

A

It can cause cyclobutane pyrimidines dimers (CPD)

The most common result is thymine dimers

58
Q

On which atoms can the thymine dimers form

A

Formed by one bond between the c6 of one thymine and c4 of the other (6-4)

Called 6-4PPs

Or two bond between the c5 and C6 of the two thymines

(6-5)

59
Q

What is the likelihood of dimer formation in UB induced damage

A

TT&raquo_space; TC > CT > CC

60
Q

What is the result of dimer formation due to uv light

A

Causes a kink in the DNA so DNA pol stalls and cant replicate

61
Q

What is a diesease caused by TT dimer formation due to UV light

A

Skin cancer

62
Q

Aside from forming dimers what can ionizing radiation also do

A

The high energy causes the radiolysis of water which makes ROS

These ROS can cause base loss (AP sites), strand breaks

And dna protein cross links (dna and transcription factors are cross linked which stops gene expression)

63
Q

What are intercalating agents and what do they do

A

They are chemicals that mimic the base pairs and intercalate between them

They cause the dna pol to skip that region of dna and make indel and frameshift mutations

Also change the dna topology by stretching them

64
Q

What are examples of intercalating agents

A

Proflavin, ethidium bromide

65
Q

What is hydroxylation and the result

A

Adding a hydroxyl group to the amino of cytosine

Makes hydroxylaminocytosine (HC)

HC binds to adenine

So C:G to T:A

66
Q

What are the base analogs

A

5-bromouracil

2-amino purine

67
Q

What is 5-bromouracil (5-BrU)

What does the keto form pair with

What does the enol form pair with

A

A thymine analog which exists in the keto and the enol form

Keto form pairs with adenine (no effect since stil T:A)

Enol pairs with G

68
Q

What is 2-amino purine (2-AP)

A

An adenine analog

When 2-AP is protonated at N1 it pairs with C

69
Q

What are alkylating agents

Where does alkylation most readily occur

A

They are thing that introduce alkyl groups

Occurs most readily at nucleophillic centres of the nucleotides

Prefer GC rich regions to attack

N7 guanine O6 GUANINE N3 adenine

70
Q

When an aplkylating agent alkylates a base, when does it have the most affect

A

After replication, that’s when it becomes a mutation and bases get mismatched

Then through more replication the mutations can get amplified

71
Q

What are alkylating agents examples

A

EMS

EES

MNNG

Nitrosamine

Nitrosourea (used to introduce mutations)

72
Q

What can also get alkylated by ems

A

O6 of guanine

O4 of thymine

73
Q

When researchers use EMS to alkylate something what type of mutation it it and why is it helpful

A

It’s usually a substitution mutation (GC to AT)

Can induce a mutation using EMS to the organism and observe the outcome of the phenotype of the organism then attribute the change in phenotype to the function of the gene

74
Q

What naturally occurring agents can be used to introduce inter strand and dna protein cross linking

A

Uv, ionizing radiation, bifunctional alkylating agents (such as psoralens)

75
Q

What is psoralen

A

A naturally occurring compund from plants that is highly sensitive to light

When added to dna, you expose it to light, the psoralen gets activated

Cross linking agent that cross links the pyrimidines bases between two strands, links

Stops cell division

76
Q

How can psoralen be used as a treatment

A

Since it stops cell division though making kinks

It’s used in PUVA (psoralen uv a) treatment of skin problems like psoriasis eczema and vitiligo

77
Q

What dna damaging agents can be used in chemotherapy

A

Alkylating agent

Crosslinker like cisplatin (which is an alkylating agent)

78
Q

What does cisplatin do in chemotherapy

A

It’s causes dna damage by adding alkyl groups to the bases

Damages the mitochondrial dna (its own type of dna)

This activates cyt c which triggers the apoptosis pathway which causes the cell to die

This kills the cancer cells since they are more likely to take up cisplatin

79
Q

What are the classes of repair mechanisms

A

Direct reversal of DNA damage

80
Q

What are the classes of repair mechanisms

A

Direct reversal of dna damage

Base excision repair

Nucleotide excision repair

81
Q

What is the direct reversal of DNA damage used for

What is included in it

A

Small common damage

The mismatch repair system

Photoreactivation of pyrimidines dimers

Removal of a methyl group (from alkylation) by methyl transferase

82
Q

What is included in. Base excision repair BER

A

The nitrogenous base is removed, then repair happens

Specific for one type of damage base

83
Q

What is included in nucleotide excision repair

A

The nucleotides is/are removed, then repaired

General to many types of damage and is used to repair a larger region

84
Q

what organisms have MMR systems

When can the MMR happen

A

It’s conserved in prokaryotes and eukaryotes

It repairs simple dna lesions (so first Gen mismatch), so once the lesion is replicated it can’t repair

85
Q

What is the limitation of MMR

A

Misinsertions and short indels can’t be repaired

Only small changes

86
Q

In every _____ nucleotide dna pol causes ___ mismatch

But in ecoli how does the MMR help

A

Every 10^6

Cause 1

Is makes it so every 10^9 or 10^10 nucleotides has a mutation because MMR repairs it

87
Q

What is the first step in MMR system in e.coli

A

If a mismatch by dna pol 111 happens

There is a palindromic sequence in the ecoli strands : GATC

The newly made strand gets recognized by DAM methylase

DAM methylase methylated the adenine residue in the GATC sequence in the parent strand of the dna

There is a split second where the daughter strand is not methylated (this is hemimethylation)

This lets the repair enzymes distinguish the parent strand from the daughter strand

88
Q

If muts is mutated what happens

A

You get lots of mutations in. Ecoli because it’s essential for the MMR system

89
Q

What are steps 2-5 of the MMR system in ecoli

A

MutS forms a complex with mutL on the dna

The MutS/L complex scans the dna bidirectionally to find the mismatch and forms a loop where the mismatch is

Once they find the mismatch, the complex recruits MutH to cleave at the unmethylated GATC (on the daughter strand)

Then MutS/L complex recruits UvrD (helicase II) to unwind the dna in the direction of the mismatch

When unwound, the strand with the mutH cleavage is dangling and an exonuclease comes and chews off the end with the mismatch

90
Q

In MMR, when cleavage of the daughter strand at the 3’ end of the hemimethylated site (on the parent strand) happens what exonuclease gets recruited

A

A 5-3 exonuclease (since the end of the nick is the 5’ end on the daughter strand)

RecJ or exonuclease VII

91
Q

In MMR, when cleavage of the daughter strand at the 5’ end of the hemimethylated site (on the parent strand) happens what exonuclease gets recruited

A

A 3-5’ exonuclease since the end of the nick is the 3’ end of the daughter strand

Exonuclease 1 or exonuclease X

92
Q

What is steps 6 and 7 of MMR system (after the exonuclease degrade the mismatch)

A

The single stranded gap in the daughter strand is coated with single stranded DNA binding protien (SSB)

This lets dna pol III come in and fill in the proper sequence, and the nick is sealed by ligase

93
Q

What is the MMR system like in eukaryotes

A

They have proteins that are homologous to MutS and MutL But

They lack homologs to MutH and DAM methylase

They dont use methylation to distinguish between parent and daughter strands

94
Q

What are CPD photolyases

What is the chain length

Where are they found

Where are they not found

A

An enzyme which catalyzes the monomerization of CPD dimers

A single polypeptide chain of 454 to 614 amino acids

Found in bacterial, archeal, and eukaryotic cells.

Not found in placental mammals

95
Q

What is the structure of CPD photo Lyase

A

Has two noncovalently bound chromophores

These chromophores absorb sunlight , meaning it needs the sun to be active and pull apart the dimers

96
Q

How does the E. coli has CPD photo Lyase actually use sunlight to pull apart the dimers

A

It binds FADH

Also has MTHF or 8-HDF chromophores

MTHF or 8-HDF absorbs light and transfer electrons from the light to FADH

Then FADH cleave the cyclobutane ring (dimers)

97
Q

What gene encodes the CPD photolyase

What domains does it have

What is its expression in wildtype cells

A

phr (photoreactivstion) gene

Aplha helical domain, alpha beta domain, a secondary pocket (for FADH to bind)

Low expression of phr

98
Q

What happens if the phr gene is mutated

A

No CPD photolyase activity

Sensitive to UV exposure (since cant repair the dimers)

So dna replication stalls: grow slowly and have low viability

99
Q

What domain of the photolyase can harness the sun energy

A

The alpha helix domain which has the MTHF region

100
Q

What is the process of CPD photolyase direct reversal repair

A

The photolyase binds to the thymine dimer in the presence of light

Once bound it flips the TT dimer into its active site pocket using the phosphate backbone as a hinge

The MTHF absorbs a photon from light, then transfers the energy to FADH in the catalytic site

The excited FADH transfers electrons to the dimer, splitting it into two T (pyrimidines)

The electron returns to the flavin radical and forms FADH. The CPD photolyase enzyme leaves

101
Q

What type of reversal mechanism is the CDP photolyase repair

A

One step

102
Q

What is o6 methyl guanine

What does it pair with

What mutation does it cause

So what need to happen

A

A guanine that has been alkylated at O6

T

GC to AT transition mutations

Before the lesion turns into a mutation is need the because fixed

103
Q

How does direct reversal of O6 methylguanine happen

What organisms is it in

A

The methyl group of o6 meG is transferred to a cysteine residue

In the enzyme O6 meG dna methyl transferase

This corrects the o6 me guanine to regular guanine

All organisms

104
Q

What happens to the methyltransferase enzyme after direct reversal of O6 me guanine

A

Since it has been modified by taking in the methyl, it degrades itself

105
Q

What is included in excision repair

A

BER

NER (repairs indels, more nucleotides)

106
Q

More simple lesions can be repaired by

A

MMR

BER

direct reversal of dimers or o6me guanine

107
Q

What does BER repair

A

Single damaged nucleotides

SsDNA breaks

108
Q

How is prokaryotic/bacterial BER done

A

The damaged base is recognized by DNA glycosylase

DNA glycosylase hydrolyzes the N-beta-glycosyl bond (glycosidic bond) between the base and the agitate of the back bone

This makes an AP site (a basic site)

The ssDNA at the AP site is cleaved by AP endonuclease

AP endonuclease (since inside the strand) cleaves the DNA backbone at the AP site and makes a nick and released the 3’ OH and 5’ DRP (deoxyribose phosphate)

109
Q

In prokaryotic BER what happens after the AP endonuclease makes a nick

A

The segment of the DNA is removed and sealed by the nick translation activity of Pol I

Then dna ligase seals the remaining nick

110
Q

What is the nick translation activity of Pol I

How can it be used to label the dna

A

The dna pol 1 has two activities

Able to be an exonuclease to remove nucleotides (in this case 5-3 since 5’ end is floating up)

Also adds nucleotide from the 5-3 end

It’s a technique that use to label the dna fragment since the dntp that it adds during nick translation can be labelled

Then when repairing these get added and the dna is labelled

111
Q

The DNA glycosylase is _____

What does this mean

A

Conserved

Meaning all organisms have some type of glycosylase for BER that recognize diff types of damage bases

112
Q

If cytosine gets deaminated and turn to uracil

What bacterial glycosylase will do BER on it

A

Uracil DNA glycosylase (UDG)

It works only on dna since lesion that make uracil only happen on dna

Not work on RNA

113
Q

What are each of the human glycolsylases and what do they fix

A

UNG (uracil dna N glycosylase) :
ssU, U:G, U:A

TDG (thymine DNA glycosylase)

MPG (methyl purine DNA glycosylase)

OGG1 (8-oxoguanine-glycosylase):
8-oxo-G

MYH (MutY homolog):
A:G, A:8-oxoG

NTH1 (endonuclease 3 homolog)
T-glycol, C-glycol

114
Q

What happens in eukaryotic BER

A

The first two step are the same

But after the AP endonuclease makes the nick there is two pathways:

Long patch repair

Short patch repair

115
Q

What is the eukaryotic BER long patch repair

A

the eukaryotic polymerase doesn’t have the 5-3 nick translation exonuclease activity

So the 5’ DRP end peels up

And flap endonuclease chops it off and fills in the gap

Then ligase seals the nicks

116
Q

What is the eukaryotic BER shirt patch repair

A

The polymerase beta only fills in the gap from the damaged nucleotide

The ligase seals the nicks

117
Q

Since the nitrogenous bases in BER are facing inward

How can the DNA glycosylase recognize the damage and flip out the damaged base

A

It scans the minor grooves of the helix in search of kinks

Kinks caused by the damaged base not matching perfectly with the other base

When lesion is recognized the dna bends a bit then the base gets flipped out

But the adjacent bases are not disrupted

118
Q

What does NER repair

A

Bulky damaged bases

Indels
Generally big lesions

119
Q

What how does nucleotide excision repair work in prokaryotes

How many nucleotides is the gap

A

The UvrA and UvrB complex scans the DNA helix for damage

When a lesion is encountered, UVRA leaves, UVRB melt the two dna strands

UVRB recruits UVRC excinuclease (excision endonuclease)

UVRC makes a 5’ and 3’ nick on either side of the damaged nucleotides (damage in between both ends of cut)

This makes a 12-13 nt ssDNA gap

UVRD helicase releases the 12-13 nt fragment by unwinding the dna

DNA pol 1 and ligase fill and seal the gap

120
Q

What is the biggest difference in NER

A

UVRC Making two cuts

Helicase unwinds the helix to remove the entire fragment

121
Q

How does NER happen in eukaryotes

How long of a gap is there

A

XPC scans for and recognizes the lesion

XPB AND XPD are recruited to the lesion and separate the DNA to make a ssDNA bubble

After bubble, RPA binds to the bubble and positions XPF and XPG on either side of the lesion

XPF and XPG are nucleases

XPG cleaves on the 3’ side and XPF the 5’ side

A larger 24-32 nt fragment is displaced

The PCNA clamp recruits a DNA pol to fill in the gap which is then sealed by ligase

122
Q

What is transcription coupled DNA repair (TCR)

A

When there is unrepaired dna damage and transcription is starting

The damage is recognized by the RNA polymerase

The rna pol stalls at the site of the lesion

When stalled, the pol leaves and recruits the NER proteins

123
Q

What region of DNA would have the most TCR repair

A

The regions that are most highly transcribed

124
Q

Is the RNA pol proofreading ability as strong as dna pol proofreading?

A

No

125
Q

What is xeroderma Pigmentosum (XP)

A

A autosomal recessive disease

It has a defective NER system where uv damage can’t be repaired

So the skin cells are very photosensitive

Leading the early onset skin cancer

126
Q

What causes unequal crossing over of chromosomes and what does it lead to

A

If the chromosomes are not aligned properly during recombination, there will be unequal crossing over

This causes a duplication on one chromosome and deletion in the other

Leading to loss or enhancement in the phenotype

127
Q

What causes unequal crossing over of chromosomes and what does it lead to

A

If the chromosomes are not aligned properly during recombination, there will be unequal crossing over

This causes a duplication on one chromosome and deletion in the other

Leading to loss or enhancement in the phenotype

128
Q

In a paracentric chromosme what is the long arm and what is the short arm called

A

Long is Q

Short is P

129
Q

What are balanced rearrangements and the types

A

Paracentric inversion

Pericentric inversion

130
Q

What is paracentric inversion

What is the result

A

An inversion of genetic content in the chromosome(so before A BCD now A CBD)

But the genetic content is the same so in the parent (carrier) there is no phenotype change

But during recombination in the offspring, four types of gamete are made

Balanced: ABCD, A CBD

Inviable: ABCA (a repeat) with two centromeres or DBCD (d repeat) with no centromere

131
Q

In para centric inversion what invisible chromosomes are made and what is the cause

A

Either acentric (none) or dicentric (2) chromosomes

Lead to unstable chromosomes and unviable offspring

132
Q

What happens in pericentric inversion

A

Crossing over of pericentric chromosomes causes unbalanced gametes to be made

They make duplicated or deficient segments of the genes near the inverted segment (ABCA OR DBCD)

So it can make four gametes with balanced, balanced, unbalanced, unbalanced chromosomes

But still one centromere in each

133
Q

What is DSBR (double stranded break repair)

What is a backup to it

A

Double stranded break happens due to radiation, If not repaired cell will die

Since diploid cells, homologous recombination with the other chromosome can repair the damaged DNA

So an allele on the homologous chromosome can be used as a template to replace the sequence on the damaged chromsome

134
Q

How does DSBR get fixed

A

The double stranded broken chromosme goes through a set of cleavage

This cleavage makes 3’ overhangs

The 3’ overhang invades into the template strand (the homologous chromosome)

This lead to two outcomes:

SDSA or DSBR

135
Q

What is SDSA in DSBR

A

Synthesis dependent strand annealing

The two homologous chromosme are separated and there is no crossing over event

136
Q

What is DSBR in DSBR

A

Invasion happens and the dna gets repaired

But either non crossover or crossover dna is formed

137
Q

What is NHEJ (non homologous end joining)

What is the problem

A

The homologous chromosme is not always there to act as a template

KU70/80 binds at each end of the DNA the is broken

Other proteins are recruited and the two ends are ligated together

Since forcing the two ends together, if the breakage caused deletion of DNA that deletion would stay

MUTATIONS STILL PERSIST

138
Q

What is translesion DNA synthesis

A

The dna is replicating a damaged dna strand

DNA pol stalls during replication due to a lesion at the replication fork

The replisome complex dissociates from the DNA

Another DNA pol belonging to the Y family is recruited

139
Q

What happens in translesion DNA synthesis (TLS) when the Y family polymerase is recruited

A

This dna pol has doesn’t have proof reading ability so forgiving to dna damage

They will continue the replication with the mutation

The mismatch can be repaired later

140
Q

What is the end result of TLS

A

The damage is still there in the dna

But the cell doesn’t die since if it just stopped replicating it would have died

Allows survival with the mutation rather than just dying

Cmmb 411 (6 decks)

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