DNA damage and mutation #2

Question 1

What are the causes of DNA damage?

Answer 1

~ DNA replication errors
~ endogenous DNA damage
~ induced damage

Question 2

DNA replication errors

Answer 2

~ tautomerisation

~ indels

Question 3

Tautomerisation

Answer 3

~ bases adapt rare tautomeric form in template or incoming nucleotide
~ form non-watson and Crick base pairs = incorrect base pairing

Question 4

Indels

Answer 4

addition or deletion occurring from looping out errors
~ looping out in new strand = addition
~ looping out in old strand = deletion

Question 5

Endogenous DAN damage

Answer 5

~ depurination
~deamination
~ alkylation
~ oxidative DNA damage

Question 6

Depurination

Answer 6

~ deprivation of G leaves apurinic site (APsite) with no base attached to deoxyribose = premutagenic legion
~ leads to random base substitution or skipping = leads to deepyrimidination

Question 7

Deamination

Answer 7

~ deamination of C = U (not found in DNA)
~ turned into T –> GT pairing after replication
~ G-T recognising enzymes remove the combo

Question 8

Alkylation

Answer 8

~ addition of alkyl groups to bases by endogenous alkyl donors
~ modification may effect base-pairing properties

Question 9

Oxidative DNA damage

Answer 9

~ attack by reactive oxygen species (ROS)
~ high mut. rate in mit. genomes
~ damaged bases = strand breakage = replication block

Question 10

Induced damage

Answer 10

~ base analogs
~ base-modifying agents
~ inter calculating agents

Question 11

Base analogs

Answer 11

e.g. mutagenic effect of 5-bromouracil (5BU)

~ incorporated into DNA like a T but shift to C in rare state

Question 12

Base-Modifying agents

Answer 12

~ nitrous acid = deaminates bases (C–>U, A–>G)
~ hydroxylamine = hydroxylates bases (C–>T)
~ MMS = methylates bases (G–>A)

Question 13

Intercalculating agents

Answer 13

introduce frame shift
e.g. ethidium bromide
~ flat planar = inserts groove in DNA helix