Genomic Dysfunction Flashcards
What is the “central dogma” of genetics?
DNA- transcription-RNA-translation-protein
Why is DNA condensed during the cell cycle?
To prevent DNA damage when it is being separated
What amino acids primarily compose a histone protein and why is this ideal?
The primary AAs are arginine and lysine which give the protein a more positive charge. This complements the negatively charged backbone of the DNA strand.
What is the main difference between euchromatin and heterochromatin?
euchromatin is less packed than heterochromatin. This occurs because euchromatin is more actively transcribed than the rest of the genome.
What year was the DNA structure released by Watson and Crick?
1953
What is RNA splicing?
A piece of transcribed RNA that is altered post-transcription. Introns will be excized out and exons will be spliced together to form different genes.
What is HDAC?
Histone Deacetylace- will remove acetyl group from lysine residue on histones to deactivate the section of DNA
What is HAT?
Histone Acetyl Transferase- Adds an acetyl group to the histone protein to activate the DNA.
Methylation
Adds methyl group to the DNA molecule which will repress gene expression
Hypermethylation
Will cause transcriptional silencing and can be inherited by daughter cells during cell division
Topoisomerase
relieves overwound supercoils during DNA transcription
Irinotecan
Topoisomerase- I inhibitor- used in colorectal cancer
Etoposisde
Topoisomerase- II inhibitor- used in leukemia
What do topoisomerase inhibitors do?
block the cell cycle; create single and double brand breaks; leads to apoptosis and cell death
What kind of DNA damage does UV radiation cause?
pyrimidine dimers form
Depurination
loss of a purine from DNA strand
Deamination
loss of an amine group from the nucleotide-
Adenine to hypoxanthine
Guanine to xanthine
Cytosine to uracil
What is direct repair of DNA damage?
corrects with DNA photolyase or methylguanine methyltransferase depending on the type of damage (pyrimidine dimers or O6-methylguanine
Base excision repair
correction of single base mismatches or nondistorting alterations- corrected using DNA glycolases
Nucleotide excision repair
Chemical adducts that distort DNA- corrected using NER protein complexes, DNA polymerase and DNA ligase
Mismatch excision repair
mismatched base in daughter strand- corrected using MER protein complexes, DNA polymerase and DNA ligase
Recombination repair
Double strand breaks- corrected using multiple different systems
Transcription coupled repair
stalled RNA polymerase during transcription
xeroderma pigmentosum
Defects to the NER complex leading to sensitivity to light
Hereditary nonpolyposis colorectal cancer
Defects to the MER complex
Breast Cancer/ BRCA1
defects from recombination repair
Cockayne Syndrome
Mutation to the ERCC6 and ERCC8 genes that result in defects to the TCR repair system
