Functions and Dysfunctions of Genomic Regulation Flashcards
What effect does acetylation have on chromatin?
It opens the chromatin and transcriptionally activates it.
What residues of histone proteins are targets for post translational modification?
Lysine residues
How many histones are in each nucleosome core particle?
8 histone proteins
What does DNA polymerase require to begin processing?
A free 3’-OH
What is miRNA?
A biological process in which RNA molecules inhibit gene expression, or translation.
What is the significance of long terminal repeats (LTRs)?
Formed by reverse transcription of retroviral RNA. Used by viruses to insert their genetic material into the host genomes.
What are topoisomerase and what is its clinical significance?
Breaks phosphodiester bond in DNA to relieve supercoiling created my replication. Drugs that target topoisomerase are used as anti-cancer drugs.
What are nucleoside analogue inhibitors and how do they work?
They are nucleoside analogues that lack the 3’-OH. Because of this, they arrest DNA synthesis by acting as chain terminators. Can be used to treat cancers and viral infections.
Describe the effect of UV radiation (non-ionizing radiation) on DNA.
Can produce a covalent linkage between two adjacent pyrimidines (T-T or C-T), creating pyrimidine dimers.
Describe the effect of ionizing radiation on DNA.
It can lead to double strand breaks, chemical modification of bases, and DNA-protein cross-links.
What are the two main types of spontaneous DNA damage?
Depurination and deamination
What are the different types of deamination?
Adenine to Hypoxanthine
Guanine to Xanthine
Cytosine to Uracil
Where are CpG Islands found and what is its role in gene expression?
They are found in the promotor regions of DNA. Methylation of CpG islands stably silences genes.
What carcinogen is a metabolism product following the consumption of well done meat? What is its pro-carcinogen?
Carcinogen: BPDE
Pro-carcinogen: benzo[a]pyrene
What are the different types of chemical agents that can cause DNA damage?
Cross-linking agents, alkylating agents, and intercalating agents.
What is Thalidomide?
An intercalating agent. Initially used as an anti-anxiety medication, but later found to cause birth defects.
What are the symptoms of Xerderma pigmentosum (XP) and what repair pathway is affected by it?
UV sensitivity and increased rate of skin cancer. Defect in nucleotide excision repair.
What are the symptoms of hereditary nonpolyposis colorectal cancer (HNPCC) and what repair pathway is affected by it?
Increased rate of colon cancer. Defect in mismatch excision repair.
What are the symptoms of Cockayne syndrome and what repair pathway is affected by it?
Neurodegenerative disorder characterized by growth failure, photosensitivity, and premature aging. Defect in transcription coupled nucleotide excision repair.
How is HNPCC inherited?
In an autosomal dominant manner.
A mutation in what enzyme and repair mechanism can cause breast cancer?
BRCA2, repair by homologous recombination
Describe nucleotide excision repair.
Used to repair chemical adducts that distort DNA. NER complex removes stretch of DNA and DNA polymerase fills in the gap. Ligase seals nicks.
Describe mismatch excision repair.
Used to repair incorrect base in newly synthesized daughter strand. MER complex binds DNA with mismatch and removes region. DNA polymerase fills in the gap. Ligase seals nicks.
What is the consequence of non-homologous end joining following a double strand break?
One or more nucleotides will be lost in the process
What is rifampicin?
An antibiotic that inhibits bacterial RNA synthesis. It has a side effect of increasing the metabolism of other drugs.
What is the significance of DNA methylation occurring at gene promoter CpG islands?
It blocks transcription and can be inherited by daughter cells following cell division.
What is the significance of ubiquitin in protein degradation?
When bound to a protein, it signals a proteasome to digest the protein into peptides.
Describe SUMO-Targeted Ubiquitin Ligases (STUbLs).
Contains a RING domain that puts ubiquitin on proteins. Also contains SUMO-interacting Motifs (SIMs) that interact with SUMO.
