DNA Replication, Mutation, and Repair Flashcards
Cyclin and Kinase that leads to Progression past the (G1) Restriction Point at the G1 / S boundary
Cyclin: D
Kinase: CDK4, CDK6
Cyclin and Kinase that leads to the initiation of DNA synthesis in Early S Phase
Cyclin: E. A
Kinase: CDK 2
Cyclin and Kinase that leads to the transition from G2 to M phase
Cyclin: B
Kinase: CDK1
Involves the removal of an amine group from the DNA base
Deamination
Deamination causes unnatural DNA bases through a reaction with ___
H2O
Unnatural bases
Adenine -> ____
Guanine -> ____
Cytosine -> ____
Hypoxanthine
Xanthine
Uracil
Involves the removal of a purine from the DNA base through hydrolysis
Depurination
Alkylating agents can add a methyl or ethyl group to a nitrogenous base
Alkylation of Base
Nitrogen, sulfur mustard, methyl and ethyl methane sulfonate are examples of
Alyklating Agents
Can lead to transition, transversion, and frame shift mutations
Alkylation of Base
Interchange of a purine to another purine, or of a
pyrimidine to another pyrimidine in DNA (similar bases)
Transition
interchange of a pyrimidine to a purine or of a purine to a pyrimidine in DNA (dissimilar bases)
Transversion
a mutation caused by insertion or deletion of bases that alters the reading frame for codons
Frame Shift Mutatioon
Derivatives of normal bases are incorporated into the DNA
Base-Analog Incorporation
5-bromouracil, 2-aminopurine, 6-mercaptopurine, and acycloguanosine
are examples of
Base-Analogs
____are molecules that take the place of the normal nitrogenous
bases in DNA (A, T, C, G)
Base analogs
What causes linkage of adjacent thymine bases along the DNA strand? Type of damage?
UV Light; Thymine-Thymine dimers
Alkylating agents that can cause cross-linkages that are either interstrand or intrastrand
Bifunctional Alkylating Agent Cross-Linkage
chemotherapeutic drugs such as cyclophosphamide are an example of
Bifunctional alkylating agents
an cause single strand or double strand breaks due to ionizing radiation, radioactive disintegration of backbone element, and oxidative free radical formation
Chain breaks
Examples of this cause of chain break are gamma rays, x-rays that sever strands
ionizing radiation
What can oxidative free radical formation do?
Can modify purines, creating 8-hydroxy-deoxyguanosine
Marker of oxidative damage to DNA
8-OH-dG
Cross linkages can happen between three things
Intrastrand, Interstrand, Between DNA and protein molecues
A chromosomal abnormality wherein there’s a break in one particular chromosome, and that chromosome will then fuse to a different
chromosome, which will lead to what we call a fusion product
Translocations
Sometimes pieces from two different chromosomes will trade places with each other (National Cancer Institute, n.d.)
• May lead to medical problems such as leukemia, breast cancer, schizophrenia, muscular dystrophy and Down Syndrome (National Cancer Institute, n.d.)
A molecular process that increases the number of copies of a gene sequence without a proportional increase in the other genes
Gene Amplification
Gene amplification leads to (2)
− Overproduction of the protein (Alberts, et al., 2015)
− Enhanced expression of the genes in the amplified portion (Mondello, et al., 2010)
plays an important role in cancer
proteins that identify damages or breaks in the DNA
sensors
phosphorylates mediator or effector proteins to influence cell activity
transducers
intermediary proteins for repair response
mediators
dictate and carry out the ultimate outcomes of DNA damage response
effectors
A potent CDK-Cyclin inhibitor which causes cell cycle arrest
p21
Effectors of cell death (apoptosis)
PUMA, BAX, and NOVA
An effector for cell aging (senescence)
Cell aging (senescense)
Recognition of distortion in DNA by ___ → ____ dsDNA into
ssDNA and removes affected area → ____ adds bases through addition of phosphodiester bonds → ____seals the nick between the new nucleotides and the old strand
what type of repair?
uvrA, helicasel dna polymerasel dna ligase; Nucleotide Excision Repair
Damaging agent of Nucelotide Excision Repair
UV light chemicals
Corrects a single mismatched base pair
Mismatch repair
____ recognizes mismatched base pair → ____ removes
area of mismatch → ____ adds bases through addition of phosphodiester bonds → ____ seals the nick
what type of repair?
MutS Protein; Exonuclease; DNA Polymerase; DNA ligase; mismatch repair
Damaging agent of mismatch repair
replication errors
Single base repair
base excision repair
____ recognize the damaged base and remove it → ____ recognize the site with a missing base → AP Endonuclease cleaves the sugar-phosphate backbone → ____ removes the sugar-phosphate that lacks the base → ____ repairs the damaged DNA → ____ seals the nick
what type of repair?
DNA glycosylases ; AP
endonucleases; Deoxyribose phosphodiesterase; DNA polymerases; DNA ligase ; base excision repair
Damaging agent of Base Excision Repair
oxygen radicals, hydrolysis, alkylating agents (Rodwell et al., 2018)
• For cells in the S and G2 phases of the cell cycle
• There is a need for the daughter strands to repair the double strand
breaks of the parent strand
Homologous recombination
Damaging agent of Homologous Recombination
ionizing radiation, x-rays, anti-tumor drugs (Rodwell et al., 2018)
cross linking of the daughter strands with the parent strand
holliday junction
Used during the G0 and G1 phase of the cell cycle
• Does not require the daughter strands for damage repair
Non-homologous end joining
• Has the least fidelity
____binds around the broken ends → Ku recruits DNA PKcs which
recruits the protein artemis and phosphorylates it → artemis trims residual single stranded tails from the break → ligase IV joins the broken ends together
what type of repair
Ku proteins; non homologous end joining
