Sarsour- Functions/Dysfunctions of Genomic Regulation

Question 1

What causes spontaneous DNA damage?

Answer 1

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)

Question 2

What are direct & indirect DNA damage?

Answer 2

Direct: Bonds break
Indirect: H2O hydrolysis & free radical formation

Question 3

What is UV-induced DNA damage?

Answer 3

Formation of pyrimidine dimers

Question 4

What are the two types of chemically induced DNA damage?

Answer 4

Agents that act directly to modify DNA & agents that require metabolic activation

Question 5

What type of chromosomal mutation can cause Down Syndrome?

Answer 5

In 4% of Downs cases, it is caused by a translocated chromosome

Question 6

What are DNA transposons and retrotransposons?

Answer 6

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

Question 7

What are single-nucleotide polymorphisms?

Answer 7

Common inherited change in a single base pair that occurs in at least 1-5% of the population.

Question 8

What is base excision repair (BER)?

Answer 8

Single-base mismatches & small, nondistorting alterations. Spontaneous depurination & deamination. Uracil, 8-oxoguanine, 3-methyladenine, abasic sites

Question 9

What is xeroderma pigmentosum?

Answer 9

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

Question 10

What is cockayne syndrome?

Answer 10

A transcription coupled repair (TCR). Autosomal recessive. Mutant genes ERCC6 & ERCC8. neurological delay. Photosensitivity. Progeria (premature aging). Commonly hearing loss & eye abnormalities

Question 11

What is the damage from a transcription coupled repair mechanism?

Answer 11

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

Question 12

What causes hereditary nonpolyposis colorectal cancers?

Answer 12

Lynch syndrome. Mutations in one of the alleles of genes in the MER complex. Accumulation of unrepaired DNA damage lead to genomic instability –> Cancer

Question 13

What is the damage caused by mismatch excision repair?

Answer 13

MER

During DNA replication. Mismatched nucleotide occasionally gets inserted into newly synthesized daughter strand

Question 14

What damage is caused by recombination repair?

Answer 14

Double strand breaks & radiation & chemical. Two types: Nonhomologous end joining (NHEJ) and homologous recombination (HR)

Question 15

What is a silent mutation?

Answer 15

Codon changed may code for the same AA

Question 16

What is a missense mutation?

Answer 16

Changed codon may code for a DIFFERENT AA (Ex: Sickle cell anemia)

Question 17

What is a nonsense mutation?

Answer 17

Changed codon may code for a termination codon. (Ex: Bo thalassemias)

Question 18

What is a frameshift mutation?

Answer 18

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)

Question 19

Define epigenetics

Answer 19

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)

Question 20

What is the importance of gene methylation/what is it?

Answer 20

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

Question 21

What is imprinting?

Answer 21

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

Question 22

Define Fragile X syndrome

Answer 22

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