Dna Repair Mechanisms

Front 1

what are the five types of dna repair pathways

Back 1

direct reversal repair, BER, NER, MMR, DSBR

Front 2

discuss direct reversal repair

Back 2

involves the direct reversal of the alkylation lesion of O6 methyl-guanine . O6 MGMT enzyme remove the lesion by transferring the methyl group to its oown cysteine, which inactivates the enzyme and is then degraded

Front 3

what is base excision repair used for (what types of damagge?>) List the two types

Back 3

oxidative damage, depurination, deamination, ssbr, alkylation. Pathway is either short patch or long patch repair. (short patch consists of mono and bi functional enzymes)

Front 4

describe the mechanism of short patch BER, mono functional

Back 4

DNA glycosylase used is UDG which removes the damaged base and leaves an AP site. APE1 cleaves phosphodiester bond, and a 5'dRP is left. 5'dRPase removes the drp and allows for polB to synthesze correct base. Ligase 3 repairs nick in backbone.

Front 5

describe the mechanism short patch BER, bifunctional

Back 5

DNA glycosylases NEIL1, OGG1, and NTH remove damaged base leaving AP site. 3'lyase cleaves phosphodiester bond, leaving 3' ddr5P. 3' PDE cleaves ddr5P, leaving rooom for polB to synthesize correct strand, then ligase 3 seals nicks

Front 6

describe the mechanism of long patch BER

Back 6

bakup pathwy when modified base is reistant to activity of polB. requires many of the same steps, but some important diffs. DNA glycosylase, APE 1 used, then polB gets stuck. PARP is relay master to initiate polD/E due to polB being stuck. PCNA used in conjunction with polD/E and RFC to elongate correct sequence of ncltds. FEN1 removes flap of incorrect sequencess, ligase 1 seals nick

Front 7

nucleotide excision repair used to remove what type of damage?

Back 7

bulky lesions due to uv radiation (dimerization), inter and intra strand crosslinks, some oxidative damage. main pt is that this repair mechanism repairs helical distortions.

Front 8

What are the two sub-pwys for NER

Back 8

GLOBAL GENOME NER= non transcribing strnd and transcriptionally silent areas, and transcriptional coupled repair (trnscribing strand)

Front 9

mismatch repair is used to repair what type of damage?

Back 9

base mismatches, replication errors which cause IDLs and frameshift mutations

Front 10

how does mismatch repair work?

Back 10

recognition of dna strand containing the error, exonuclease degrades strand past the damage and re-synthesizes new strand again

Front 11

describe double stranded breaks repair. what type of damage does it repair, and what two types of repair does it use?

Back 11

repairs damage caused by ionizing radiation and ROS. uses homologous recombo repair (error free) and non homologous end joining (error prone). homologous recombo is prevalent in G2 and S phase of cell cycle.

Front 12

8oxo-dg causes what type of dna damage?

Back 12

at-gc transversions. inversely related to lifespan, increases wwith age. mt dna is primary site of 8 oxo-dg damage

Front 13

properties of alkylating agents?

Back 13

mustard gas is an example. alkylated dna does not coil or uncoil properly. leads to inter and intra strand cross links. alkylated bases are base analogs

Front 14

interstrand crosslinks are repaired by _____ and _______

Back 14

MMR AND NER

Front 15

ionizing radiation causes _______. also leads to formation of ______ -______ crosslinking upon exposure.

Back 15

double strand breaks. thymine-tyrosine.

Front 16

DNA DSBS are highly ________. can lead to chromosome translocations, esulting in _____, ______ or ______chromosomesq

Back 16

recombinatorial. can lead to chromosome translocations, resulting in gene fusions, acentric or dicentric chromosomes.

Front 17

histones contain what amino acid?

Back 17

lysine rich in H1. histone is basic= positively charged. since dna is neg charged, allow for ionic bonding to form nucleosome structure

Front 18

What histones compose the octamer?

Back 18

h2a-h2b dimer + h3-h4 dimer= tetramer. two sets form octamer. H1 connects dna strands from outside (stabilize the solenoid structure)

Front 19

chromatin remodeling uses what two types of modifications?

Back 19

atp driven and covalent enzyme modification (acylation, methylation, etc)

Front 20

why modify histones?

Back 20

alter structure to provide binding sites for dna replication, transcription. or, modify to inactivate genes.

Front 21

chromasomes are made up of three structures. discuss the features of all three structual components

Back 21

nucleosome-beads on a string, 1:6 ratio. chromatin fiber= zigzag or solenoid models, 1:40 ratio. loops of chromatin fiber= 1:10k ratio

Front 22

BER of 8-oxo G using OGG 1. characteristics of OGG1

Back 22

OGG1 is constitutively expressed. two forms present, alpha in nu, and beta in mt. common polymorphism is associated with increased risk for cancer and type 2 diabetes. bi-functional , lyase activity

Front 23

types of endogenous dna damage

Back 23

base damages (depurination, base deamination), oxidative damage, replication errors (tautomerization), methylation

Front 24

base deamination cause by

Back 24

attack of water

Front 25

mammalian cell cycle checkpoints (kinases to prevent mitosis)

Back 25

ATM AND ATR kinases are activated when dna breaks are sensed to prevent mitosis

Front 26

immunoglobin recombination

Back 26

site specific recombination. joining of vdj segments in a 1:1 ratio determines the type of iGg molecule that is formed.