Telomeres Flashcards
What are telomeres?
Repetitive DNA structures at the end of eukaryotic linear chromosomes. They protect the ends from DNA repair machinery.
Do prokaryotes have telomeres?
No because their chromosomes are circular.
What is the probable reason that eukaryotes evolved linear chromosomes?
Linear chromosomes can generate great genetic diversity through independent assortment and crossing over in meiosis. This diversity is advantageous.
What would be the outcome of a singular cross over with 2 circular homologous chromosomes, each with 2 sister chromatids?
One large circle, joined at the crossover points of 2 homologous sister chromatids would be generated. This larger circle would still be attached to 2 smaller circular sister chromatids at the 2 centromeres. (Lecture 14, slide 3).
Segregation of this one structure in meiosis would generate 2 random DSBs.
What would be the outcome of an even number of cross overs with 2 circular homologous chromosomes?
The circular chromosomes would not be joined and segregation in meiosis would be successful.
What could evolve to solve the requirement of an even number of crossovers in circular chromosome meiosis?
- Counting of the crossovers. Maybe too complex?
- Linearisation of chromosomes (successful segregation with any number of crossovers). WHAT HAPPENED (eukaryotes).
In a circular chromosome, what does a DNA end mean?
A DNA break (DNA damage).
In a linear chromosome, what does a DNA end mean?
- A DNA break (DNA damage).
- The end of the chromosome (natural end).
How are natural and broken DNA ends distinguished in linear chromosomes?
Presence or absence of telomeres.
Is the DDR activated by telomeres?
No.
What is the DNA damage response (DDR)?
- Phosphorylation cascade
- Triggers cell cycle arrest
- DNA repair enzymes recruited to break site and subsequent NHEJ or HDR (uses sister chromatid)
- OR apoptosis
What would happen if DDR was activated at all DNA ends (including telomeres)?
A DSB could lead to a dicentric chromosome (a telomeric end is used to repair the break, so 2 chromosomes are ligated). This leads to another DSB when these chromosomes are segregated.
What would happen if telomerase was activated at all DNA ends (including DNA breaks)?
There would be terminal deletions of DNA no longer joined to a centrosome. I.e. genetic information is lost after meiosis.
What are the possible DNA sequences of telomeres (non-coding)?
- Long inverted terminal repeats (LITRs)
- Short tandem repeats (STRs)
What are the possible structures of telomeres?
- LITRs with covalently closed single stranded hairpin
- LITRs with terminal protein bound to the 5’ end
- LITRs with ss 3’ overhangs
- STRs with ss 5’ overhangs
How can telomeres vary between organisms?
- Sequence
- Structure (RNA and protein)
- Telomere binding proteins (TBPs)
What are the functions of TBPs?
- Hide the DNA end from DNA repair enzymes, preventing the DDR and cell death.
- Recruit telomerase.
What are the classes of TBPs present in most organisms?
- Recognise dsDNA
- Recognise ssDNA
Which organisms have 3’ overhang telomeres?
- Vertebrates
- Budding yeast
- Fission yeast
What is the name of the TBP complex in humans?
Shelterin
How many proteins does shelterin consist of?
6
How are human telomeric ends protected?
- TBPs (shelterin)
- T loop formation
What is a T loop?
3’ ssDNA base pairs with sequence earlier in the telomere so a loop forms.
Which organism has 5’ overhang telomeres?
C. elegans