Function & Dysfunction of Genomic Regulation Flashcards
(GENOMIC ALTERATION)
Transposons
- “jumping genes”
- mobile sequences of DNA that change position within the genome of a single cell
- copy/cut -> paste
- can reverse mutations that are there or create new ones
(GENOMIC ALTERATION)
SNPs
- common inherited change in 1 BP
- not actually a mutation but can present as one
- used as markers in mapping of genomes - indicates increase risk of a certain disease
- polymorphisms (changes in SNPs) may be associated with increase susceptibility to disease
- can be used in drug development
What type of DNA repair mechanism is responsible for the repair of double stranded breaks?
Recombination Repair
(DNA REPAIR)
Base Excision Repair
- used for small, single base problems
- spontaneous depurination and deamination
- repair process:
(1) altered base recognized by DNA Glycosylasas
(2) DNA Glycosylases remove base, AP Endonuclease cuts phosphodiester bond, AP Lyase removes deoxyribose phosphate
(3) DNA Polymerase β replaced excised nucleotide
(4) DNA Ligase seals nick
(DNA REPAIR)
Nucleotide Excision Repair (NER)
- used for damage due to: chemical adducts (BPDEguanine adducts, cisplatin adducts), alteration in DNA shape in the local area, UV damage
- repair process:
(1) NER complex recognizes distortions and nicks DNA on both sides of damage sites
(2) Removal of stretch of damaged DNA
(3) DNA Polymerase ε fills in gaps
(4) DNA Ligase seals nick
(DNA REPAIR)
Mismatch Excision Repair (MER)
- damage occurs during DNA replication when the wrong nucleotide gets inserted into newly synthesized daughter strand
- repair process:
(1) MER Complex binds to DNA and recognizes mismatch in daughter strand
(2) Removal of damaged section of daughter strand by MER complex
(3) DNA Polymerase δ fills gap
(4) DNA Ligase seals nick
(DNA REPAIR)
Recombination Repair
- repairs double strand breaks and radiation/chemical damage
- 2 types: non-homologous end joining, homologous recombination
What type of genetic mutation results in the formation of a stop codon?
Nonsense
What are the 4 major types of genomic alterations?
The Cats Get Snuggles
- Transposons
- Chromosomal mutations
- Gene amplification
- Single nucleotide polymorphisms (SNPs)
What disease is caused by a transposon genomic alteration?
Hemophilia A
- hereditary bleeding disorder caused by a lack of blood clotting factor VIII
- transposon L1 is inserted into factor VIII gene which renders factor VIII ineffective
(GENOMIC ALTERATION)
Chromosomal Mutations
- includes: deletions (chromosome segment lost), translocation (segment from chromosome is transferred to another), duplication (segment from one chromosome transferred to its homologous chromosome which gives it a duplicate of some genes), inversion
- Ex: translocations can cause down syndrome – translocated chromosome 21
(GENOMIC ALTERATION)
Gene Amplification
- typically occurs in S phase when one gene gets duplicated – results in 4 copies of gene so when cell divides each daughter cell will have 2 copies of the gene
- can be a result of all the other genomic alterations
- also can be caused by impaired replication
- can be good: more copies of gene means less mutational effects in evolution
- can be bad: cancer, cancer therapy resistance
What are the 3 major ways DNA is damaged?
- Spontaneous
- Physical agents: Radiation
- Chemical agents
Spontaneous DNA Damage
- happens daily
- most frequently happens thru depurination (purine removed from nucleotide and now only have backbone) or deamination (lose an amine on nucleotide, impacts transcription)
What are the two type of physical agents that lead to DNA Damage?
- Ionizing Radiation
- Non-ionizing Radiation
Ionizing Radiation
- due to gamma radiation
- leading cause of double strand break
Non-Ionizing Radiation
- due to UV light (requires NER for repair of DNA)
- leading cause of pyrimidine dimers – esp thymine dimer