Chapter 11 repair Flashcards
The most direct way to repair DNA lesions is to identify and then reverse the DNA damage, proofreading activity of _______ can fix some errors immediately
DNA polymerase
3’ -> 5’ exonuclease activity
Pyrimidine dimers can be directly repaired by _______ in bacteria single-celled euks, plants, and some animals
- but not humans :(
photoreactive repair
The enzyme _______ uses energy from visible light to break the bonds between pyrimidine dimers
photolyase
What is photolyase encoded by in Ecoli?
phr (photoreactive repair) gene
DNA damage by_______ is repaired by enzymes that remove the added chemical groups, restoring the nucleotide to its normal form
alkylating agents
Enzymes that repair DNA damaged by alkylating agents are called _______
alkyltransferases
Alkyltransferases are permanently _______ after one repair/conversion reaction
ex) O6-methylguaninemethyltransferase
inactivated
_______ is a multistep process that may repair damage to a nitrogenous base or replace an incorrect base
Nucleotide base excision repair (BER)
What are the steps to base excision repair (BER)? (4)
1) DNA glycosylases recognizes bp mismatch and removes incorrect bp creating an AP site
2) AP endonuclease creates nick on 5’ side
3) Nick translation occurs replacing several nucleotides
4) ligase seals the backbone
_______ is often used to repair UV-induced damage to DNA so it is also known as ultraviolet repair
Nucleotide excision repair
What are the 4 proteins that are involved in UV-damage repair?
uvrA, uvrB, uvrC, uvrD
What are the steps to UV repair? (5)
- also known as NER
1) UVR AB complex bind opposite of photoproduct
2) UVR A disassociates and UVR C binds
3) UVR BC complex cuts 3’ and 5’
4) UVR D helps remove the DNA fragment
5) DNA polymerase and ligase fix the strand
UVR D (a _______) helps remove the DNA fragment containing the photoproduct
helicase
Xeroderma Pigmentosa is caused by mutations of any of seven different genes involved in _______
NER
mismatched nucleotides that escape DNA polymerase proofreading may be detected and repaired by ________
mismatch repair
In mismatch repair, repair enzymes distinguish between the original, correct nucleotide and the new, mismatched nucleotide using the presence of _______ on the original strand
methylation
What are the 3 proteins specified for mismatch repair?
1) MutH
2) MutS
3) MutL
What are the steps to mismatch repair? (7)
1) MutH binds to hemimethylated DNA region
2) MutS binds to DNA mismatch
3) MutL forms complex with MutS and the complex binds to MutH
4) MutH protein breaks phosphodiester bond on 5’ end of unmethylated daughter strand (~GATC)
5) exonuclease enzymes digest nucleotides from the “nick”
6) DNA polymerase and DNA ligase fill in the gap
7) Dam methylase methylates adenine of GATC of daughter strand
Biochemical mechanisms to recognize the presence of _______ and initiate a _______ consist of a tightly regulated genetic process
DNA lesions
repair response
_______ plays a pivotal role in communicating DNA damage, to activate the transcription of the _______ gene
ATM
p53
The p53 repair pathway controls cell responese to mutation by deciding to either: (2)
1) pause the cell cycle (g1-s phase)
2) initiate apoptosis
p53 initiates G1 arrest by inducing synthesis of _______ that inhibits formation of cyclin-CDK complexes
p21
p53 also activitates transcription of _______ gene, which encodes a slowly acting inhibitor of _______
possible apoptosis
BAX gene
BCL2
In damaged cells, if the p53-induced pause of the cell cycle persists too long, the _______ pathway is induced when BCL2 is inhibited
apoptotic
The ________ system can be activated in response to heavily damaged DNA in E.coli cells
SOS repair
SOS repair is accomplished by activation of translesion or bypass polymerases (_______)
DNA pol V
How does SOS repair work? (3)
1) Rec A proteins coat the template strand ahead of the lesion (forms DNA-RecA-SSB-complex)
2) DNA pol V replaces pol III
3) Once normal replication can occur DNA pol III replaces pol V
What are the two mechanisms that carry out repair on double-stranded break repair?
1) non-homologous end joining
2) synthesis-dependent strand annealing (HDR)
Nonhomologous end joining allows cells to _______ the ability to complete DNA replication, though the process inevitably leads to mutation. When does NHEJ usually take place?
regain
after G1 before DNA replication (S)
What is the process of nonhomologous end joining?
1) double stranded break in DNA
2) PKcs, Ku70, and Ku80 complex attach to the broken ends of DNA
3) the complex trims free ends of the break
4) blunt ends ligated by ligase IV
what are the 3 proteins that make up the complex in nonhomologous end joining?
1) PKcs
2) Ku70
3) Ku80
Double-stranded breaks that occur after replication can be repaired by an error-free process called _______
synthesis-dependent strand annealing
synthesis-dependent strand annealing is also known as _______
homology dependent repair (HDR)
What are the steps to SDSA? (4)
1) broken edges are trimmed
2) Rad51 is attached to broken ends and intact sister chromatid
3) Strand invasion process creates displacement (D) loop
4) sister chromatids reform and fixed strands are annealed with original fragment
