Genomic Regulation Flashcards
• Euchromatin
Lightly packed form of chromatin, highly enriched in genes, often under active transcription, most active form of the genome
• Heterochromatin
very condensed, genetically inactive, contains few active genes, position effect: Activity of an active gene is silenced if moved near heterochromatin
• Histone Acetylation
modifying enzymes involved in histone acetylation are called histone acetyltransferases, promotes gene expression
• Histone Methylation
the transfer of one, two, or three methyl groups from S-adenosyl-L-methionine to lysine or arginine residues by histone methyltransferases
• Phosphorylation-
compaction is achieved by repeatedly folding chromatin fibers into a hierarchy or multiple loops and coils, accomplished by phospholylation of Histone H1
• Helicase
Unwinds DNA helix, bind and hydrolyze ATP, 1000bp/sec
• Topoisomerase
Relieves overwound supercoils, every 10 bp replicated corresponds to one turn, used as a target in anti-cancer drugs
Nucleoside analog inhibitors (Correlation box)
- DNA synthesis involves the formation of 3’ to 5’ phosphodiester bonds, nucleoside analogs that lack the 3’-OH group act as drugs that inhibit DNA replication
- Such nucleosides need to be converted to dNTPs before they can act as inhibitors of DNA polymerase
- Ex: arabinosylcytosine (treatment of leukemia)
i. Ionizing radiation (X-rays)
- 40 to 60 chemically distinct base damages
- Direct strand breaks
- DNA-protein cross-links
ii. Non-ionizing (UV light)
- Inducing formation of a covalent linkage between adjacent pyrimidine bases
- There are two outcomes
- Pyrimidine cyclobutane dimers (common)
- 6-4 covalent linkage of two pyrimidines (p53 cells)
iii. Spontaneous Mutation
- Depurination: 5000 purine lost
- Deamination: C to U change 100 bases/day
- Adenine becomes hypoxanthine
- Guanine becomes Xanthine
- Cytosine becomes Uracil
- Outcomes: DNA Replication Ensues or Base deletion or substitution
i. Direct repair
- Type of damage repaired: Pyrimidine dimers, O6-methylguanine
- Enzymes associated: DNA photolyase, Methylguanine methyltransferase
ii. Base excision repair
- Type of damage repaired: Single-base mismatch
* Enzymes involved: DNA glycolases, AP endonuclease, AP lyase, DNA polymerase, DNA ligase
iii. Nucleotide excision repair
- Type of Damage repaired: Chemical adducts (Nitrogen mustard, cisplatin, DMS, MMS) that distort DNA
- Enzymes involved: NER protein complex, DNA polymerase, DNA ligase
- Disease: Xeroderma pigmentosum
iv. Mismatch repair
- Type of damage repaired: mismatched base in daughter strand
- Enzymes involved: MER complex, helicase/endonuclease, DNA polymerase, DNA ligase
- MutS binds while MutL scans for nick and triggers degradation of the nicked strand
- Disorder: Hereditary nonpolyposis colorectal cancers