L17-DNA damage & repair. Flashcards
Name all types of dan repair systems.
A) mismatch repair
B) base repair excision
C) nucleotide excision repair
D) DNA strand break
explain the mismatch repair system
mismatch repair system corrects errors that escape form the proofreading process during DNA replication
what are MUT proteins?
they are proteins that mediate the process of mismatch repair.
when does mismatch repair occur?
within seconds of dan replication and it reduces error form 1 in a million to 1 in a billion.
what are the 2 steps of the mismatch repair?
A) recognition of mismatch strand
B) repair procedure
explain the recognition of mismatched strand process
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.
explain what happens during the repair procedures
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
what the clinical implications for the mismatch repair?
mutation o mut proteins in humans are associated with hereditary nonpolyposis colorectal cancer
when is the base excision repair system used?
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.
what are the 2 stages of base excision repair?
A) abnormal base removal
B) recognition and repair of the AP site.
explain the events that occur during the abnormal base removal process
special enzyme called DNA glycosylases recognizes the mismatched bases and hydrolytically cleaves the deoxyribose phosphate backbone forming a gap called AP site.
explain the events that take place during the AP site recognition and repair.
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
when is nucleotides excision repair mechanism is demonstrated?
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
why is the dimerization of 2 thymines is dangerous?
because this dimerization is bulky and prevents DNA polymerase to replicate the DNA beyond the site of dimerization.
what are the stages of nucleotide excision repair?
A)recognition and excision of uv light induced dimers
B) Repair
explain the events that occur during recognition and excision of uv induced dimers.
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.
explain the events that occur during the repair stage
DNA polymerase III and DNA ligase completes the repair process
what are the clinical implications for nucleotides excision repair system?
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
what are the causes of double strand break mutation?
ionizing radiations, chemotherapeutic agents like doxorubicin and oxidative free radicles.
what are the 2 mechanisms used to repair DNA breaks?
homologous recombination and non-homologous
explain the homologous recombination mechanism
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.
explain the non homologous recombination
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
what are the clinical implications for double strand break repair mechanism?
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.
