Sarsour- Functions/Dysfunctions of Genomic Regulation Flashcards
What causes spontaneous DNA damage?
Cell environment is not static, metabolic activity, DNA replication is not perfect. Happens on daily basis. DNA is surrounded by active chemistry. (Ex: depurination, deamination)
What are direct & indirect DNA damage?
Direct: Bonds break
Indirect: H2O hydrolysis & free radical formation
What is UV-induced DNA damage?
Formation of pyrimidine dimers
What are the two types of chemically induced DNA damage?
Agents that act directly to modify DNA & agents that require metabolic activation
What type of chromosomal mutation can cause Down Syndrome?
In 4% of Downs cases, it is caused by a translocated chromosome
What are DNA transposons and retrotransposons?
DNA transposons: DNA/RNA is copied & cut then pasted into incorrect region of genome which renders issues
Retro is similar but the RNA gets reverse transcribed then put somewhere it shouldn’t be
What are single-nucleotide polymorphisms?
Common inherited change in a single base pair that occurs in at least 1-5% of the population.
What is base excision repair (BER)?
Single-base mismatches & small, nondistorting alterations. Spontaneous depurination & deamination. Uracil, 8-oxoguanine, 3-methyladenine, abasic sites
What is xeroderma pigmentosum?
Genetic disorder of DNA repair in which patients carry mutations in the nucleotide repair enzymes mostly on an endonuclease. High sensitivity to sunlight. pigmentary skin changes. autosomal recessive. Defects in NER complex. Prone to developing melanomas & squamous cell carcinomas
What is cockayne syndrome?
A transcription coupled repair (TCR). Autosomal recessive. Mutant genes ERCC6 & ERCC8. neurological delay. Photosensitivity. Progeria (premature aging). Commonly hearing loss & eye abnormalities
What is the damage from a transcription coupled repair mechanism?
RNA polymerase stalls at a lesion in DNA. TCR proteins called ERCC-6 & ERCC-8 recognize the stalled RNA polymerase and recruit other repair proteins
What causes hereditary nonpolyposis colorectal cancers?
Lynch syndrome. Mutations in one of the alleles of genes in the MER complex. Accumulation of unrepaired DNA damage lead to genomic instability –> Cancer
What is the damage caused by mismatch excision repair?
MER
During DNA replication. Mismatched nucleotide occasionally gets inserted into newly synthesized daughter strand
What damage is caused by recombination repair?
Double strand breaks & radiation & chemical. Two types: Nonhomologous end joining (NHEJ) and homologous recombination (HR)
What is a silent mutation?
Codon changed may code for the same AA
What is a missense mutation?
Changed codon may code for a DIFFERENT AA (Ex: Sickle cell anemia)
What is a nonsense mutation?
Changed codon may code for a termination codon. (Ex: Bo thalassemias)
What is a frameshift mutation?
Reading frame is altered due to one or two nucleotides being added or deleted from the coding region of a message sequence (Ex: Cystic Fibrosis)
Define epigenetics
Changes that do not affect the DNA sequence of the genome. Affected by the environment. Alterations in gene expression that are stably inherited. Two main types of modification (gene methylation & histone modification)
What is the importance of gene methylation/what is it?
Important for tissue specific gene expression. Methylation of a gene is called imprinting. Methylation of 5’-CG-3’ residues in DNA is thought to cause steric hindrance to the binding of proteins that influences gene expression
What is imprinting?
When silencing of genes on chromosomes is a result of gene methylation. Have the ability to be turned on or have the ability to be turned on or off depending on which parent contributed the gene that has been silenced
Define Fragile X syndrome
Caused by mutation of the fragile X mental retardation gene on the long arm of the X chromosome. Symptoms include mild-to-moderate intellectual disability, problems with social interactions & delayed speech, physical features that include long & narrow face, large ears, flexible fingers, & large testicles
