Dna Mutations And Repair

Front 1

what is the mechanism for
genome mutations
chromosome mutations
gene mutations

Back 1

genome- nondisjunction, 10-2
chromosome- chromosome rearrangements 6x10-4
gene- single base sub 10-10 bp

Front 2

define transition

Back 2

pur to pur or
pyr to pyr
eg T-C

Front 3

define transversion

Back 3

pur to pyr or
pyr to pur
eg T-G

Front 4

define missense
nonsense
silent

Back 4

misense- changes AA in protein
nonsense- premature stop codon
silent- no change in AA seq

Front 5

what causes frameshift mutation?

Back 5

insertion or deletion of one or more base pairs

Front 6

define in-frame

Back 6

insertion or deletion in multiples of 3 bp

Front 7

define tandem repeated DNA
what are egs

Back 7

insertion of repeats
eg Fragile X > 230 CGG repeats
eg Huntington's >40 CAG repeats

Front 8

define tautomerization; how does it cause mutations?

Back 8

interconversion of isomers by proton rearrangements
cause erroneous base pairings that generate substitutions following a round of DNA replication

Front 9

cytosine can be deaminated to form what base?
5 methylcytosine?

Back 9

cytosine-->uracil
5 methylcytosine-->thymine

Front 10

define hotspots

Back 10

substitution to thymine can NOT be recognized by DNA repair machinery therefore 5 mCG 3 sites are hotspots- more than 30% of all single base changes have occured here

Front 11

what produces apurinic (AP) site in DNA?

Back 11

removal of a purine base and replacing with OH

Front 12

what are eg of mutations caused by depurination?

Back 12

transitions and transversion
bp deletions
DNA strand breaks

Front 13

what type of spontaneous mutation involves hotspots?

Back 13

single nucleotide runs are hotspots for insertion

Front 14

what type of mutation does HNO2 cause and via what process?

Back 14

induced mutations (environmental) via deamination

Front 15

what can alkylated G pair with? what can alkylated G cause?

Back 15

T, causing transition (c-->t)
alkylated G can cause depurination

Front 16

define intercalating agents; what can they lead to? what is another process that can do this?

Back 16

aromatic molecules that insert between bases and stretch DNA double helix
can cause insertions
addition of bulky chemical groups also leads to distortions

Front 17

eg of DNA damage by free radical involving guanine; what is another example of hydroxyl free radical damage?

Back 17

hydroxyl radical generates 8 hydroxy guanine which causes transversion and binds with A instead of C
-can cause DNA strand breaks resulting in deletions of 1 or more bp when break is repaired by non homologous end joining

Front 18

what can UV rays cause?

Back 18

formation of covalent dimers in form of cyclobutane ring between adjacent thymines in DNA strand, distorting double helix and impairs from DNA replication and transcription

Front 19

what protein recognizes mismatched base pairs?

Back 19

MutS- prokaryotes
hMSH2- humans

Front 20

what is function of MutL (hMLH1 in humans)

Back 20

activates MutH which cleaves new daughter strand in vicinity of mismatch
directs excission of oligonucleotdie with MutS, Helicase and Exonuclease

Front 21

what fills in gap and what seals strand?

Back 21

DNA pol 1 fills (beta in humans) and ligase seals strand

Front 22

what is role of DNA glycosylases in base excision repair?

Back 22

scans along DNA, cleaves N-glycosidic bond to generate free base and AP site

Front 23

what enzyme breaks DNA backbone by cleavage of phosphodiester bond after glycosylases?

Back 23

AP endonucleases

Front 24

what enzyme removes deoxyribose and creates free 3'OH and 5'P?

Back 24

deoxyribosephosphodiesterase

Front 25

what are eg of repair by base excision repair?

Back 25

deamination of adenine to form hypoxanthine and oxidation of guanine to form 8 hydroxyguanine
-removes and replaces base

Front 26

what is function of nucleotide excision repair?

Back 26

recognize and repair damage or lesions that cause distortions in DNA double helix

Front 27

what complex is used in nucleotide excision repair? what is the function of the proteins?

Back 27

excinuclease complex
-recognize damage, helicases unwind damaged region, cleavage by 5 and 3' endonucleases on both sides of damage
followed by replacement and sealing by beta polymerase and ligase

Front 28

define transcription coupled repair and its significance

Back 28

nucleotide excision repair for actively transcribed genes thus cells maintain integrity of expressed genes preferentially

Front 29

what 2 proteins are involved in transcription couple repair?

Back 29

CSA and CSB

Front 30

describe process of transcription coupled repair

Back 30

stalling of RNA polymerase as it encounters eg thymine dimer
CSA and CSB recognize stalled RNA polymerase and it is displaced and transcription is terminated
excinuclease complex is recruited by CSA and CSB to initiate nucleotide excision repair

Front 31

define recombinatorial repair and its process- what is the significance?

Back 31

repair double strand breaks by homologous recombination- RESTORES ORIGINAL SEQ
-homologous chromosome is not damaged and recombination followed by gaps filled by beta poly and ligase form holliday junctions which are cleaved and religated to restore DNA seq

Front 32

what proteins are involved in recombinatorial repair?

Back 32

RecA (Rad51 in humans)
RuvA, B, C