DNA mutations and repair

Question 1

what is the nature of a mutation

Answer 1

errors can arise during DNA replication; failure to repair lesions results in a mutation which alter the sequence of bases in a gene.

Question 2

whats the diff bet a mutation in prokaryotes vs eukaryotes

Answer 2

1. for prokaryotes a mutation affects the only copy of the genetic info available and passes it to the next generation.
2. eukaryotes; somatic mutations can affect tissues but are not heritable. Mutations in germ cells that predispose to cancer can be inherited.

Question 3

Somatic mutations are ___, many mutations have minimal effect. and initially only one cell is affected. Somatic mustions are only harmful if they result in a ____of mutant cells

Answer 3

inevitable; clone

Question 4

Turning a normal cell into a malignant cancer cell requires ___specific mutations in one cell

Answer 4

6

Question 5

what are four major types of mutations

Answer 5

1. Substitution
2. Deletion
3. Insertion
4. Rearrangement
   - deletions, insertions and rearrangements often occur together

Question 6

what are the types of substitution (point) mutations

Answer 6

1. silent: no change in aa
2. missense: change in aa
3. nonsense: change in DNA makes change in mRNA which intro termination codon, you get shorter protein
4. frameshift: delete/insert one of the bases that change everything from there on

Question 7

what is a transition substitution

Answer 7

purine for purine, pyrimidine for pyrimidine

Question 8

what is a trasversion substitution

Answer 8

purine for pyrimidine, or pyrimidine for purine

Question 9

what is the most common mutation in cystic fibrosis

Answer 9

deletion of one codon (for phenylalanine)

Question 10

What are causes of mutations

Answer 10

1. Errors during DNA replication: tautomer formation causes substitution
2. Chemical modification: mutagens causes substitution
3. intercalation: of chemical mutagens bet bases cause insertions or deletions
4. double strand breakage: radiation, certain mutagens causes rearrangements and deletions

Question 11

Nitrous acid reacts with ___containg amino groups and causes oxidative deamination and can result in AT–>GC transitions.

Answer 11

bases

Question 12

bases are not 100% stable; spontaneous ____modifications can occur

Answer 12

chemical

Question 13

mustard gas is considered an alkylating agent which donates alkyl groups to bases and changes pairing properties of base by:

Answer 13

adds carbs to base which changes pairing properties

Question 14

What can intercalation cause

Answer 14

Introduces an obstacel to replication; Distorts how DNA looks and can block DNA resplication and RNA transcription

Question 15

what can radiation cause

Answer 15

Xray exposure causes DS breaks in DNA resulting in rearrangements, deletion. UV exposure causes thymine dimers that interfere with replication

Question 16

what are mutation repair systems

Answer 16

1. Mismatch repair; mostly due to tautomer formation
2. Base excision repair; looks for abnormal bases
3. nucleotide excision repair; large structure changes
4. direct repair; repair single base

Question 17

how do the enzymes for base excision repair work

Answer 17

take out base and leave sugar backbone which leaves AP site rec by endonucleases which cleave DNA from that site with DNA polymerase 1 and DNA ligase

Question 18

whats a pattern seen in mutation repair enzymes

Answer 18

Recognition, excision, and repair

Question 19

whats special about ABC exinuclase

Answer 19

recognition and excision from same enzyme

Question 20

whats special about O6 methylguanine DNA methyltransferase

Answer 20

takes methyl group off guanine (to own specific cysteine) and accept it on methyltransferase enzyme

Question 21

In E.Coli there are enzymes that detect mismatch:

Answer 21

MutS: detects mismatch
MutL: complexes with mismatch
MutH; recognizes sequence that is methylated

Question 22

how does mismatch repair occur in E. coli

Answer 22

Parent strand seps; hemimethylated state at GATC sites which can be rec by MutH which will cleave unmethylated seq. Fill it with Dna pol III and seal with ligase

Question 23

what does defect in human mismatch repair system lead to:

Answer 23

hereditary nonpolyposis colorectal cancer

Question 24

All cells have ___ ____ that remove abnormal bases in a DNA strand from their attached sugar and leave AP site. specific ___ ___ cuts sugar out and repair system fills in gap

Answer 24

DNA glycosylases; AP endonucleases

Question 25

In humans, defect of the human thymine dimer repair system leads to autosomal recessive disease called

Answer 25

xeroderma pigemntosum; ind have high sensitivity to skin damage by UV light and strong predisposition to skin cancer.

Question 26

Direct repair is more efficient. ___ dimers can be repaired by light induced reverse reaction catalyzed by ____

Answer 26

pyrimidine; photolyases

Question 27

what is the process affected and phenotype of hereditary nonpolyposis colorectal cancer

Answer 27

mismatch repair; colon cancer

Question 28

what is the process affected and phenotype of xeroderma pigmentosum

Answer 28

nucleotide excision repair; skin cancer, UV sensitivity, neurological defects.