L17-DNA damage & repair.

Question 1

Name all types of dan repair systems.

Answer 1

A) mismatch repair
B) base repair excision
C) nucleotide excision repair
D) DNA strand break

Question 2

explain the mismatch repair system

Answer 2

mismatch repair system corrects errors that escape form the proofreading process during DNA replication

Question 3

what are MUT proteins?

Answer 3

they are proteins that mediate the process of mismatch repair.

Question 4

when does mismatch repair occur?

Answer 4

within seconds of dan replication and it reduces error form 1 in a million to 1 in a billion.

Question 5

what are the 2 steps of the mismatch repair?

Answer 5

A) recognition of mismatch strand

B) repair procedure

Question 6

explain the recognition of mismatched strand process

Answer 6

the mut proteins recognizes the mismatched DNA nucleotides and it differentiates between the parental strand and daughter strand by the degree of methylation, the parental strand is always methylated while the daughter strand is not.

Question 7

explain what happens during the repair procedures

Answer 7

after the mismatched segment is recognized, special endonuclease nicks the DNA and mismatched nucleotides are removed form the strand by exonuclease enzyme and additional adjacent nucleotides are removed and then DNA polymerase III and DNA ligases add nucleotides and ligates the new segment to the rest of the DNA segment

Question 8

what the clinical implications for the mismatch repair?

Answer 8

mutation o mut proteins in humans are associated with hereditary nonpolyposis colorectal cancer

Question 9

when is the base excision repair system used?

Answer 9

when bases spontaneously change like when cytosine is slowly deaminated and becomes uracil or as a result of deamination or alkylating compounds like nitrous acid and dimethyl sulphate. also bases are lost like cells lose 10,000 purines a day.

Question 10

what are the 2 stages of base excision repair?

Answer 10

A) abnormal base removal

B) recognition and repair of the AP site.

Question 11

explain the events that occur during the abnormal base removal process

Answer 11

special enzyme called DNA glycosylases recognizes the mismatched bases and hydrolytically cleaves the deoxyribose phosphate backbone forming a gap called AP site.

Question 12

explain the events that take place during the AP site recognition and repair.

Answer 12

specific Ap endonuclease recognizes the AP site and initiates the excision and gap filling process by making an endonucleolytic cut only at the 5 prime end. a deoxyribose phosphate lyase removes the single base free form the phosphate group and sugar then DNA polymerase and ligase completes the repair process

Question 13

when is nucleotides excision repair mechanism is demonstrated?

Answer 13

when the cell is exposed to uv light it causes 2 pyrimidine bases to form a covalent bon usually thymine bases and form a dimer

Question 14

why is the dimerization of 2 thymines is dangerous?

Answer 14

because this dimerization is bulky and prevents DNA polymerase to replicate the DNA beyond the site of dimerization.

Question 15

what are the stages of nucleotide excision repair?

Answer 15

A)recognition and excision of uv light induced dimers

B) Repair

Question 16

explain the events that occur during recognition and excision of uv induced dimers.

Answer 16

a uv specific endonuclease called uvrABC exinucleases recognizes the dimer and cleaves the dmaged strand on both sides 5 prime and 3 prime a short oligonucleotide segment including the dimer is excised leaving a gap in the DNA strand.

Question 17

explain the events that occur during the repair stage

Answer 17

DNA polymerase III and DNA ligase completes the repair process

Question 18

what are the clinical implications for nucleotides excision repair system?

Answer 18

xeroderma pigmentosum: genetic disorder where the cells cannot repair their DNA due to defects in nucleotide excision repair proteins causing severe sensitivity to the sun skin ulcers skin cancer and extensive accumulated mutations

Question 19

what are the causes of double strand break mutation?

Answer 19

ionizing radiations, chemotherapeutic agents like doxorubicin and oxidative free radicles.

Question 20

what are the 2 mechanisms used to repair DNA breaks?

Answer 20

homologous recombination and non-homologous

Question 21

explain the homologous recombination mechanism

Answer 21

both DNA strands are cut and a different correct DNA strand is used a s a template therefore it is less prone to errors. occurs during s phase and g2 phase only.

Question 22

explain the non homologous recombination

Answer 22

the faulty or defective strand is used as a template to synthesize the other strand and some of the DNA might be lost. can occur anytime

Question 23

what are the clinical implications for double strand break repair mechanism?

Answer 23

A) mutation of BRCA1 and BRCA2 which are proteins involved in homologous recombination makes the person more prone to breast and ovarian cancer.
B) decreased ability to repair interstand DNA might cause fanconi anemia–> anemia mental retardation and kids with this disease are prone to various types of cancer.