Telomeres/DNA damage

Question 1

end replication problem

Answer 1

progressive shortening of chromosome ends over cell division cycles - can lead to DNA damage response and cell death if not ameliorated by telomerase

Question 2

mechanisms of overcoming the end replication problem (7)

Answer 2

circular chromosomes, end recombination, telomere repeat addition, transposition to telomeres, genome concatamerization, hairpin ends

Question 3

T/F. Telomerase uses DNA template to add repeats to chr ends

Answer 3

False, it’s an RNA template

Question 4

T/F. Telomerase RNAs are conserved in sequence and share conserved structural elements

Answer 4

False, although they do share conserved structural elements, they are *not conserved in sequence and do vary in overall secondary structure

Question 5

How do short telomeres induce a DNA damage response?

Answer 5

Through ATM kinase bound to damaged region signalling p53 pathway, which leads to apoptosis and senescence

Question 6

what are cell cycle checkpoints?

Answer 6

steps at which the cell cycle will halt if conditions are not satisfied, ensure that prerequisite reactions have completed before proceeding

Question 7

what are the transducing proteins in the p53 damage response?

Answer 7

CHK1 CHK2

Question 8

T/F. Histone variants can play a role in DNA damage response

Answer 8

True, H2A.X has a proposed function in DNA damage signaling

Question 9

Where do telomerase null mutants arrest in the cell cylce?

Answer 9

At the G2/M transition, that’s where the DNA damage checkpoint is

Question 10

What is the ALT pathways?

Answer 10

Alternative lengthening of telomeres, also called “survivors” - where telomeres can be lengthened not by telomerase, but by recombination via strand invasion, elongation and repair

Question 11

T/F. Telomere shortening in vivo is noticeable within a single generation

Answer 11

False mostly, when doing KO mice it was found that many generations were needed to see a short telomere phenotype

Question 12

what are two characteristics of inherited mutations underlying short telomere syndromes?

Answer 12

autosomal dominant inheritance, genetic anticipation

Question 13

what are some mechanisms through which cancer cells can increase telomerase production?

Answer 13

TERT promoter mutations (most common), MYC amplification, TERT amp or rearrangements, loss of repressor Men1