Quiz 2- Genomic Regulation Flashcards
Cross-linking chemical agents
Nitrogen mustard, cisplatin, mitomycin C, carmustine
Alkylating agents
Dimethyl sulfate (DMS), methylmethane sulfonate (MMS)
Intercalating agents
Thalidomide
Drugs that inhibit HDACs, used as anticonvulsants and cancer drugs
Valproic acid and vorinostat
DNA methylation
Typically represses gene transcription
Acyclovir and AZT
Lack 3’ -OH group which, when added during RNA replication, acts as chain terminator in viruses
UV radiation
Can produce covalent linkage (pyrimidine dimers)
Ionizing radiation
Double strand breaks, chemical modification of bases, DNA-protein crosslinks
Non-ionizing radiation
Sunlight can cause pyrimidine dimers
Spontaneous DNA damage
Depurination (lose entire purine base, leaves sugar phosphate behind), deamination (adenine -> hypoxanthine or guanine -> xanthine or cytosine -> uracil), base deletion/substitution
Methylated cytosine residues
Stably silences genes in CpG sites/islands (happens in cancers)
Base excision repair
DNA glycosylase removes mismatched base (non-distorting mutation), AP endonuclease cuts phosphodiester bond, and DNA polymerase replaces correct nucleotide
Nucleotide excision repair
Repairs distorted DNA shape (ex dimers). Strand unwound, damage nicked out with some other nucleotides. DNA polymerase fills in gap. Defects can lead to xeroderma pigmentosum
Mismatch excision repair
MER complex binds to DNA at deformation, endonuclease cuts daughter strand w/ mutation and removes segment. Polymerase fills gap. Defects = hereditary nonpolyposis colorectal cancers
Recombination: NHEJ and homologous recombination
For when DNA undergoes double stranded breaks.
NHEJ: ends joined together by DNA ligase, several base pairs at site missing
Homologous: genetic info from other chromosome (if happened during cell division) used to repair damage. (BRCA1/2 genes)
Transcription-coupled repair
Type of NER initiated when RNA polymerase stalls at lesion in DNA template during transcription. ERcc-6 an ERcc-8 recruited (defects in these lead to cockayne syndrome severe growth defects)
Translesion synthesis (bypass synthesis)
Caused by unrepaired thymine dimers. Uses DNA polymerase to add in adenine across from one thymine. Low fidelity - still have mutations
Reduced/incomplete penetrance
Frequency that a gene manifests itself as a phenotype
Locus heterogeneity
When many genes influence a phenotype
Pleiotropy
When one gene influences two or more seemingly unrelated phenotypic traits
Variable expressivity
The range of phenotypes seen between individuals with a specific genotype
Polygenic inheritance
Traits in which variations are thought to be caused by the combined effects of multiple genes. Ex: height
Multifactorial inheritance
When environmental factors cause variation in the trait. Threshold of liability must be crossed before the disease is expressed
