MCM Final - DNA Damage and Repair Flashcards

0
Q

depurination

A

removal of a purine

- remove base from backbone
- link to deoxyribose hydrolyzed
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1
Q

spontaneous lesions

A

small chemical modification (single base pair)

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2
Q

deamination

A

cytosine changed to uracil

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3
Q

bulky lesions

A

cause a large change in DNA strand

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4
Q

covalent linkage

A

bulky lesion caused by oxidative species, UV light, or carcinogens
-cause a change in DNA helix structure

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5
Q

copy errors

A

DNA polymerase incorrectly adds base pair

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6
Q

mutagen

A

agent (physical or chemical) that causes an alteration in DNA

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7
Q

base analog

A

mutagen structurally resembles purine or pyrimidine and inserts into DNA strand

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8
Q

intercalating agent

A

mutagen that insert between double helix

usually flat with multiple rings

cause stretching of double helix and DNA polymerase adds extra bases opposite to it

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9
Q

direct acting agent

A

chemically react with DNA directly

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10
Q

indirect acting agent

A

require metabolic conversion before actively altering DNA

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11
Q

cytochrome p-450

A

mechanism by which an indirect acting agent is converted into a mutagen that can alter the DNA

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12
Q

UV radiation

A

shorter wavelengths - more energy - more damage

UV-A (320-400nm) - induces oxidative damage
UV-B (280-320nm) - induces dimers between pyrimidines (C or T)
UV-C (180-290nm) - doesn’t make it through ozone

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13
Q

ionizing radiation

A

causes ionization

- loss of electron
- unstable reactive radical
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14
Q

alpha particle

A

helium nuclei

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15
Q

beta particle

A

high speed electron

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16
Q

damage due to ionizing radiation?

A

single strand break
double strand break **
base damage
cross linking

17
Q

base excision repair

A

repair spontaneous lesions (single base pair)

1 DNA glycosylase scans DNA and removes damaged bases
2 AP endonuclease cuts phosphodiester backbone where empty base spot is
3 DNA polymerase adds nucleotide correctly
4 DNA ligase seals nick

18
Q

DNA glycosylase

A

in base excision repair

- scans DNA for damaged bases and removes them
- leaves backbone in tact
19
Q

AP endonuclease

A

in base excision repair

-cleaves phosphodiester bond where DNA glycosylase has removed a base pair

20
Q

nucleotide excision repair

A

repairs bulky lesions (larger)

1 multienzyme complex scans for distorted DNA helix
-cleaves phosphodiester backbone on either side of distortion
2 DNA helicase removes the single strand cleaved out
3 DNA polymerase adds nucleotides
4 DNA ligase seals the nick

21
Q

multienzyme complex

A

in nucleotide excision repair

-scans for distorted DNA helix and cleaves phosphodiester bonds on each side of distortion

22
Q

mismatch repair

A

correct DNA mismatches of DNA polymerase

follow behind replication
-recognize strand breaks (okazaki fragments - lagging)
MutS and MutL bind to mismatched base
-direct excison of DNA between the single strand break and mismatch

23
Q

3’ to 5’ exonuclease activity

A

proofreading during replication

-by DNA polymerase

24
Q

back-up polymerases

A

when 3’ to 5’ exonuclease doesn’t work

less accurate - take guess at what sequence should be

25
Q

transcription coupled repair

A

RNA polymerase II stalls at lesion
-on template strand only

directs repair machinery to the site

CSB recognizes stalled RNA polymerase II
TFIIH remodels RNA polymerase II
XPG cuts DNA

Lesion repaired and polymerase restarts

26
Q

double strand break causes

A

radiaton, errors, and oxidation

27
Q

non-homologous end joining

A

less accurate, ends brought together and ligated

-loss of nucleotides

28
Q

homologous recombination

A

more accurate

-sister chromatids used as a template

29
Q

Process of non-homologous end joining

A

1 Ku70/80 recognizes free double strane ends
2 recruits DNA-PK which acts as a kinase to recruit ligase
3 DNA ligase ligates the ends

30
Q

Ku 70/80

A

recognize free double strand break during nonhomologous end joining

31
Q

DNA-PK

A

recruited to double strand break by Ku70/80 during nonhomologous end joining
-act as kinase to recruit DNA ligase

32
Q

Process of Homologous Recombination

A

1 double break strands are broken to yield 3’ single strand ends
2 Rad51 pairs with 3’ overhang
-causes it to bind with sister chromatid
3 DNA synthesis occurs using sister chromatid as a template
(holliday junction is formed, but then resolved)
4 newly synthesized DNA strand then used as template for other broken strand
5 DNA ligation

33
Q

Rad51

A

binds free 3’ ends of double strand breaks during homologous recombination
-allows the end to bind with sister chromatid as template

34
Q

DNA damage checkpoints

A

G1 to S
Slow S
S to M

35
Q

ATM protein

A

generates intracellular signals in response to spontaneous DNA damage

associates with damage and phosphorylation of downstream kinases
-kinases then act on target proteins
-p53 - target usually bound by Mdm2 (destroyed)
-when phosphorylated - stimulate synthesis of p21
-bind G1/S-Cdk or S-Cdk complex and inhibit them
Chk1 and Chk2 - block activation of M-Cdk

36
Q

p53

A

inhibited when dephosphorylated by association with Mdm2

- when phosphorylated:
	- stimulates transcription of p21
		- which binds G1/S-Cdk or S-Cdk and inhibit them
37
Q

Mdm2

A

bind p53 targeting it for destruction

38
Q

p21

A

its transcription activated by p53

- binds G1/S-Cdk or S-Cdk and inhibits them
- arrest of cell cycle entry
39
Q

Chk1 and Chk2

A

block activation of M-Cdk

40
Q

Telomere shortening triggers what?

A

activation of p53

-causes cell cycle arrest