Origins of Mutations and DNA Replication/Repair

Question 1

Depurination

Answer 1

• -loss of 5,000 bases everyday
• -adenine or guanine
• -hydroylzation of bond between base and deoxyribose

Question 2

Deamination

Answer 2

• -most common one is spontaneous conversion of cytosine to uracil
• -messes things up b/c cytosine pairs w/ guanine but uracil would pair w/ adenine

Question 3

Pyrimidine Dimers

Answer 3

–caused by UV light

dimerization of adjacent thymine bases on same DNA strand

Question 4

4 Levels of Mutations

Answer 4

• -gene: single bases switches
• -chromosomal: rearrangements, deletions or duplications of chromosomal regions
• -genomic: surplus or loss of chromosomes
• -mutations impacting chromatin: changes in methylation of DNA or in modification of histone proteins

Question 5

Frequency in Types of Mutations

Answer 5

from most common to least: genomic>chromosomal>gene

Question 6

Missense vs. Nonsense mutations

Answer 6

• -missense: changes AA codon

- -nonsense: introduces stop codon

Question 7

Small insertions or deletions:

3 mechanisms?

Answer 7

• -incorrect recombination
• -strand slippage
• -intercalating agents

Question 8

Frameshift mutations

Answer 8

• -insertion/deletion not in multiple of 3 in gene

- -25% of human genetic diseases

Question 9

Importance of Homologous Crossover

Answer 9

–recombination of genetic material–constantly creating new combinations

Question 10

Chiasmata

Answer 10

–holds chromosomes together after crossing over occurs

Question 11

Anaphase

Answer 11

• -also called disjunction
• -separation of chromosomes
• -nondisjunction can occur and leads to genetic disease and increases w/ maternal age

Question 12

Problems which can occur during crossover

Answer 12

• -misaligned crossover: insertion or deletion of sections of chromosomes
• -nondisjunction

Question 13

Nondisjunctions compatible w/ life

Answer 13

• -monosomy = always fatal
• -Trisomy 13 (Patau syndrome), 18 (edward syndrome), 21 (Down) are all viable
• -sex chromosome anomalies: 47XXX, 48XXXX, 49XXXXX, 48XXXY, 49XXXXY
• -triploidy or tetraploidy always fatal

Question 14

Mosaicism

Answer 14

• -cells in single person that have different genotype
• -occurs when early on cells develop somatic mutation (during embyrogenesis)
• -2-4% of Pt. with trisomy 21 are mosaics (some cells lose 3rd chromo. 21 and develop as normal cells)

Question 15

Strand Directed Mismatch Repair

Answer 15

• -system must determine which strand is original parental strand; does this by identifying “nicks” in daughter strand
• -repair enzyme recognizes distortions in DNA helix and chews out wrong NT and DNA pol replaces it

Question 16

HNPCC

Answer 16

• -hereditary nonpolyposis colorectal carcinoma (Lynch Syndrome)
• -80% of developing colon cancer if you have the syndrome
• -caused by defects in mismatch repair system

Question 17

Base Excision Repair

Answer 17

• -DNA glycosylases recognize altered bases in DNA and hydrolytically remove them
• -specific glycosylases for specific altered bases
• -base removed then the sugar-phosphate backbone cut out

Question 18

Nucleotide Excision Repair

Answer 18

• -repairs damage by agents that result in large changes in the structure of DNA
• -pyrimidine dimers ex.
• -looks for DNA helix distortions

Question 19

Xeroderma Pigmentosum

Answer 19

–mutations that abolish or impair function of any of the proteins involved in NT excision repair (helicases, nucleases, DNA polymerase, etc.)

Question 20

non-homologous end joining

Answer 20

• -break in both strands of DNA
• -no intact template for repair
• -DNA ends brought together and ligated but some bases lost at breakpoint
• -usually doesnt effect genes since most of genome is non encoding but it can effet genes
• -common repair response to DNA double breaks

Question 21

Homologous End-Joining

Answer 21

• -since most cells are diploid recombination processes can be used to repair DNA
• -info to replace messed up DNA is found on non messed up other chromosome

Question 22

AntiCancer Agents

Answer 22

• -inhibit DNA replication and/or repair processes

- -induce apoptosis in cell

Question 23

Cytarabine

Answer 23

• -analogue of cytidine which contains arabinose (instead of ribose)
• -treatment of acute leukemias
• -inside cells is converted to cytarabine triphosphate which will compete w/ deoxyribonucleotides for binding to DNA pol.

Question 24

Cyclophosphoamide

Answer 24

• -hodgkins lymphoma, lung, breast and teste cancer
• -coverted to phosphoramide mustard in liver which is bi-functional alkylating agent
• -forms inter- and intra-strand DNA crosslinks

Question 25

Doxorubicin

Answer 25

• -board activity against lots of different tumors
• -forms tripartite complx w/ DNA and topoisomerase II enzyme
• -topoisomerase II makes double stranded DNA breaks during cell cycle and this agent prevents re-ligation of DNA strands so breaks accumulate