29 Questions
Which cellular response to DNA damage involves the activation of complex signaling networks to decide cell fate?
Apoptosis
Which DNA repair mechanism involves excision of damage?
Mismatch repair
What is the outcome determined by in pathways that dictate cell fate in response to DNA damage?
Threshold of pro-survival factors versus pro-death factors
Which DNA repair mechanism is involved in the direct reversal of DNA damage?
Mismatch repair
What is the cellular response to DNA damage that involves damage tolerance for cells that need to survive?
Translesion synthesis
Which cellular response to DNA damage can lead to cell death if the DNA damage is too great?
Apoptosis
Which cellular response to DNA damage involves cell cycle arrest?
Double strand break repair
What determines the outcome in pathways that dictate cell fate in response to DNA damage?
Threshold of pro-survival factors versus pro-death factors
Which cellular responses can occur if the cell is expendable or the DNA damage is too great?
Apoptosis
Which type of cells activate complex signaling networks to decide their fate in response to DNA damage?
Non-expendable cells
Which protein is responsible for recognizing that something is wrong with the DNA through distortions or bulky additions?
XPA
What is the main function of TFIIH in nucleotide excision repair?
Unwinds the DNA helices
Which subtype of nucleotide excision repair is defective in p53-mutant cells?
Global Genomic Repair (GGR)
In which phase of the cell cycle does Homology-directed repair (HR) occur?
G2
Which proteins are important components of Nonhomologous end joining (NHEJ)?
KU70, KU80 and DNA-PK
What is the process called when cells bypass some types of DNA damage using distinct DNA polymerases?
Translesion synthesis
Which cells repair most types of DNA damage more effectively than others?
Human embryonic stem cells
DNA repair capacity differs greatly between cell types. Which cell type is defective in base excision repair?
Monocytes and muscle cells
What can failure of DNA repair lead to?
Apoptosis
What is triggered by DNA damage response proteins ATM and ATR?
Cell cycle arrest and cell death pathways
Which enzyme is responsible for repairing damage caused by UV?
Photolyase
What is the mechanism used to repair O6-methylguanine?
Removal of the methyl group from guanine to a cysteine group in the active site of the enzyme
Which protein is responsible for recognizing the mismatched DNA and recruiting MutL protein for repair?
MSH2
What type of repair generates mutation?
Mismatch repair
Which repair mechanism tends to repair lesions that derive from endogenous sources?
Base excision repair
What is the function of Poly ADP-ribose polymerase 1 (PARP1) in DNA repair?
Recruitment of repair enzymes to single strand breaks and attachment of ADP-ribose units to DNA and repair enzymes
What is the main difference between nucleotide excision repair and base excision repair?
Nucleotide excision repair repairs lesions created by exogenous agents, while base excision repair repairs lesions from endogenous sources
What is the role of Zinc finger domain in DNA repair involving Poly ADP-ribose polymerase 1 (PARP1)?
Binding to single strand breaks and attaching multiple ADP-ribose units to DNA, histones, and repair enzymes
Which type of cancer is associated with defects in mismatch repair genes MSH2 and MLH1?
Hereditary nonpolyposis colon cancer
Study Notes
Cellular Response to DNA Damage
- Cellular response to DNA damage involves activation of complex signaling networks to decide cell fate
- Outcome determined by intensity of DNA damage, type of damage, and cellular context
DNA Repair Mechanisms
- Excision of damage involves nucleotide excision repair (NER)
- Direct reversal of DNA damage involves base excision repair (BER)
- Homologous recombination (HR) occurs in the S and G2 phases of the cell cycle
- Nonhomologous end joining (NHEJ) is involved in DNA repair during the G1 phase
- NHEJ proteins include Ku, DNA-PKcs, and Ligase IV
DNA Damage Tolerance
- Cells that need to survive use damage tolerance mechanisms
- Post-replication repair (PRR) is a damage tolerance mechanism
Cell Fate Determination
- Cell fate determined by extent of DNA damage and cellular context
- Cell death can occur if DNA damage is too great
- Cellular responses can include cell cycle arrest, apoptosis, or senescence
Protein Functions
- p53 protein is involved in recognizing DNA damage and activating signaling networks
- TFIIH is responsible for unwinding DNA during nucleotide excision repair
- MutS protein recognizes mismatched DNA and recruits MutL protein for repair
- Poly ADP-ribose polymerase 1 (PARP1) is involved in base excision repair and recruits proteins to the site of damage
- Zinc finger domain in PARP1 is involved in recognizing DNA damage
Cancer and DNA Repair
- Defects in mismatch repair genes MSH2 and MLH1 are associated with Lynch syndrome
- Defects in NER are associated with xeroderma pigmentosum
- Failure of DNA repair can lead to cancer and other diseases
Test your understanding of direct reversal, mismatch repair, and base excision repair in DNA damage response. Assess your knowledge of cellular responses to DNA damage and the principles and steps involved in DNA repair pathways.
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