DNA repair mechanisms Flashcards
what are gene mutations classified into
Hereditary (germline mutations) and Acquired (or somatic) mutations
what are the DNA repair mechanisms
- Proofreading (during replication)
- Mismatch repair (during replication)
- DNA damage repair mechanisms
what are the types of DNA damage repair mechanisms
i. Direct reversal
ii. Excision repair (base or nucleotide)
iii. Double-stranded break repair
what mammalian DNA polymerases are capable of DNA proofreading
delta and epsilon
give 7 differences between exonuclease and endonuclease
- Endonuclease separates the nucleotides into two or more fragment, Exonuclease removes the nucleotides one by one from the fragment
- Endo-nuclease cuts the nucleotide bases from the middle, exo from 5’ or 3’ end
- endo doesnt req 5’ or 3’ end, exo does
- endo- lag phase, exo- absent
- endo- sequence specific, exo- not
- endo- releases oligonucleotides, exo- nucleotides
- endo- DNA repair, blocking pathogen entry, exo- repair, proofreading, stabilization, no pathogen blocking
when does mismatch repair happen
right after new DNA has been made
what is the general function of mismatch repair
remove and replace mis-paired bases (ones that were not fixed during proofreading)
what else can mismatch repair detect
detect and correct small insertions and deletions that happen when the polymerases “slips,” losing its footing on the template
how does mismatch repair work
1) protein complex recognizes and binds to the mispaired base
2) A second complex cuts the DNA near the mismatch, and more enzymes chop out the incorrect nucleotide and a surrounding patch of DNA
3) A DNA polymerase then replaces the missing section with correct nucleotides, and an enzyme called a DNA ligase seals the gap
how can original and newly made strands be told apart in bacteria
by a feature called methylation state (old DNA has methyl on some of its bases while new doesn’t)
what recognizes the wrong match and connects
MutS
what binds to MutS to form a complex
MutL
what does MutH do
recognizes the GATC sequence which is methylation
how do MutH and the MutS-L complex
by looping
what happens after MutS-L complex merges with MutH
DNA exonuclease cuts from the methylated GATC sequence to the wrong base
________________ resynthesizes and binds the DNA ligase nucleotides
DNA polymerase III
how does O-6-methylguanine happens and how can it be repaired
addition of a methyl group to the structure of guanine by alkylating agents and can be reversed with enzymes
what enzyme repairs O-6-methylguanine
O-6-methylguanine-DNA methyltransferase (MGMT)
what is the major type of damage induced by UV light
formation of pyrimidine dimers
how do pyrimidine dimers form
joined by the formation of a cyclobutane ring resulting from saturation of the double bonds between carbons 5 and 6
what does formation of a pryrimidine dimer cause
distorts the structure of the DNA chain and blocks transcription or replication
what is a mechanism of repairing UV-induced pyrimidine dimers and why
photoreactivation (photolyase) because energy derived from visible light is utilized to break the cyclobutane ring structure
how do DNA photolyases work
DNA photolyase recognized kink in DNA and bind to site. when excited by Blue Light, photolyases change confirmation breaking a part dimer
what species has photoreactivation repair and which doesnt
e.coli, yeast and some plants and animals.
humans lack this mechanism
what enzymes play a key role in base excision repair
glycosylases
what does deamination of cytosine cause and how is this problem fixed
converts a cytosine base into uracil, and pairing uracil with guanine
the problem is fixed by DNA glycolyase which removes the base
what is nucleotide excision repair used for
corrects types of damage that distort the DNA double
helix and UV damage
how else does UV radiation affect DNA
can make cytosine and thymine bases react with neighboring bases that are also Cs or Ts, forming bonds that distort the double helix
what is the most common linkage fixed by Nucleotide excision repair
thymine dimer
what enzymes are used in Nucleotide excision repair
Excision endonuclease, OR UV-specific endonuclease
what does high energy radiation cause
doublestranded breaks in DNA (splitting a chromosome in two)
Two pathways involved in the repair of double-stranded DNA breaks are
Non-homologous end joining (NHEJ)
Homologous recombination pathways (HRP)
how does Non-homologous end joining (NHEJ work
two broken ends of the chromosome are simply glued back together by DNA ligase
why is Non-homologous end joining (NHEJ) unfavorable
This repair mechanism is “messy” and typically involves the loss, or sometimes addition, of a few nucleotides at the cut site but its better than the alternative
how does Homologous recombination work
Information from the homologous chromosome that matches the damaged one (or from a sister chromatid, if the DNA has been copied) is used to repair the break
Homologous recombination is “cleaner” than ______________ and does not usually cause mutations
non-homologous
what is Hereditary nonpolyposis colorectal cancer (Lynch syndrome)
by mutations in genes encoding certain mismatch repair proteins
what causes xeroderma pigmentosum
by mutations affecting the nucleotide excision repair pathway, thymine dimers and other forms of UV damage can’t be repaired
what is Distichiasis
double eyelashes, is a rare condition where you have two rows of eyelashes
