Exam #4: DNA Mutation, Replication & Repair Flashcards Preview

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Flashcards in Exam #4: DNA Mutation, Replication & Repair Deck (41):
1

Name three common DNA lesions

1) Depurination
2) Deamination
3) Pyrimidine Dimers

2

Somatic Mutation

A mutation that affects only the cell where the mutation occurred, and its progeny

3

Germline Mutation

A mutation that is passed to the offspring

4

Gene Mutation & Frequency

- Variation in nucleotide sequence via exchange, insertion, or deletion
- Occurs 10^-10 per base pair per cell division
- LEAST frequent

5

Chromosome Mutation & Frequency

- Rearrangement of chromosome following ds-DNA break or faulty recombination
- Occurs 6 x10-4 times per cell division
- Intermediate frequency

6

Genome Mutation & Frequency

- Missegregation or chromosomes during mitosis or meiosis that results in a surplus or loss of chromosomes
- Occurs 10-2 times per cell division
- MOST frequency & MOST devastating

7

Point Mutation

Exchange of one nucleotide for another

8

Silent Mutation

Change in nucleotide sequence DOES NOT result in a change in the amino acid sequence

9

Missense Mutation

Change in nucleotide sequence DOES result in a change in amino acid sequence

10

Nonsense Mutation

Change in the nucleotide sequence results in the generation of a STOP codon

11

List three processes that can lead to small insertions or deletions

1) Incorrect Recombination
2) Strand Slippage During Replication
3) Intercalating Agents (chemical agent)

12

Frameshift Mutation

Insertion or deletion of nucleotides alters the codon reading frame and produces a new protein

13

Meiosis

- Process by which 4 haploid germ cells are created from 1 diploid cell
- Two successive cell divisions without DNA replication

14

Crossing-over

Exchange of homologous chromosome fragments during meiosis

15

Disjunction

The pulling apart of homologous chromosomes during anaphase or meiosis

16

Non-disjunction

Incomplete separation of chromosomes during anaphase of meiosis

17

Consequences of Non-disjunction

- Germ cells with surplus chromosomes
- Germ cells missing chromosomes

18

In which autosomes is trisomy observed?

- 13, Patau Syndrome
- 18, Edward Syndrome
- 21, Down Syndrome

19

Mosaicism

- A somatic mutation in early embryogenesis causing the affected individual to harbor a significant amount of mutant cells
- Person has normal cells & other cells with mutation
- Frequently occurs in Trisomy 21

20

Proofreading Activity of DNA Polymerase

- 3'-->5' exonuclease activity of DNA polymerase gamme
- Edits the 3' end of growing DNA strand by pausing and re-reading the base pairing
- Tries again if incorrect

21

Strand-Directed Mismatch Repair

- System identifies the new strand by nicks/gaps
- Repair enzymes recognize distortion in the DNA double helix
- Chews back DNA & allows polymerase to resynthesize DNA

22

HNPCC (Lynch Syndrome)

- "Hereditary Nonpolyposis Colorectal Carcinoma"
- 80% chance of developing colorectal cancer
- Caused by defect in DNA mismatch repair system

23

Base Excision Repair

- DNA glycoslyases recognize altered base in DNA & catalyze their hydrolytic removal
- E.g. Cytosine deaminated to Uracil recognized by uracil DNA glycosylase and cut out

24

Nucleotide Excision Repair

- Repairs DNA damage caused by agents that result in large changes in the structure of DNA e.g. pyrimidine dimers
- Enzyme complex scans DNA & recognizes distortions in the double helix

25

Xeroderma Pigmentosum

- Disorder characterized by extreme sensitivity to sunlight, pigmentation changes, & skin cancer
- Caused by mutation in proteins needed for nucleotide excision repair

26

Why are ds-DNA break particularly bad?

No intact template strand remains

27

ds-DNA break repair mechanisms

- Nonhomologous end-joining
- Homologous end-joining

28

Cytarabine

- Chemotheraputic drug that inhibits DNA replication & repair
- Converted to Cytarabine Triphosphate that competes with deoxyribonucleotides for binding to DNA polymerase
- Used to treat acute leukemia

29

Cyclophosphamide

- Chemotheraputic drug that inhibits DNA replication & repair
- Used to treat Hodgkin's Lymphoma, lung, breast, and testicular cancers
- Converted to phosphoramide mustard in liver
- Bi-functional alkylating agent that causes extensive damage to DNA that can induce apoptosis

30

Doxorubicin

- Chemotheraputic drug that inhibits DNA replication & repair
- Used in a variety of cancers
- Topoisomerase II inhibitor
- Prevents re-ligation of ds-DNA breaks

31

Depurination

Loss of purine (A & G) bases because of spontaneous hydrolysis of the bond between the base and deoxyribose

32

Deamination

Removal of an amine group commonly resulting in conversion of cytosine to uracil (C-->U)

33

Pyrimidine Dimers

UV light causes dimerization of adjacent thymine bases on same DNA strand

34

What is an RNA processing mutant?

Change in nucleotide sequence changes an RNA splice site, or destroys a splice site

35

Incorrect Recombination

- One of three mechanisms that leads to small insertions or deletions
- Unequal crossover event during homologous recombination in meiosis
- Most likely at loci that contain repetitive DNA

36

Strand Slippage

- One of three mechanisms leading to small insertions or deletions
- Newly synthesized DNA in a repetitive sequence loops out in the ss-form
- Second round of synthesis results in extension or the new strand

37

How many chromosomes should be in a normal haploid germ cell?

23

38

Outline the steps of base excision repair

1) DNA glycoslyase recognizes altered base and catalyzes removal
2) AP endonuclease recognizes missing base & cuts sugar-phosphate backbone
3) DNA phosphodiesterase removes the deoxyribose
4) Gap is filled by DNA polymerase & DNA Ligase

39

Outline the steps in nucleotide excision repair

1) Enzyme complex scans DNA and finds distortion of double helix
2) Helicase separates strands
3) Backbone is cut
4) Oligonucleotide generates is peeled off
5) DNA polymerase and DNA ligase fill in the gap

40

Non-homologous end-joining

- Broken ends of DNA are brought together & ligated
- Results in loss of nucleotide/s at the break point

41

Homologous end-joining

- Recombination processes are used to repair broken DNA
- NO loss of sequence information b/c the homologous chromosome provides the template