Replication of linear DNAs Flashcards
What is the end replication problem in linear chromosomes
After synthesis of leading and lagging strand the RNA primer is removed leaving a gap in the DNA that cannot be filled. There is a 3’ overhang
More losses are sustained with each new generation
loss of an essential gene leads to cell death
What are telomeres and telomerase
Telomeres are at the ends of eukaryotic chromosomes composed of non-coding repeating sequences.
Telomerase extends the 3’ end with dNTPs, using its internal RNA molecule as a template
Telomerase extends telomeres
Why is the overhand important? Which strand has an overhang and which doesn’t?
The overhang is important for recruitment of telomere binding proteins that protect the telomeres and regulate their lengths
the lagging strand has a 3’ overhang
The leading strand is processed by nucleases into a structure with a 3’ overhang
Describe the activation of telomerase
Most cells in our body do not have active telomerase.
As these cells divide their telomeres shorten to a critical level the cell dies.
Thus most of our cells have a set limit of 40-60 divisions before they die. This causes the association of short telomeres with premature aging diseases
However, activation of telomerase is associated with immortalization of cells and with cancer.
Telomerase is activated in almost all cancers.
What is Shelterin
the shelterin complex binds mammalian telomeres. Shelterin protects and regulates telomeres. When shelterin is low, telomere elongation commences
Describe t-loops
Mammalian telomeres fold back into t-loops
When telomeres are long, the t-loop is more stable; when short, the t-loop is destabilized and telomerase can gain access for telomere elongation
Why do most bacteria have circular chromosomes
this circularity allows it to replicate without specialized structures at the ends referred to as telomeres that allow the complete replication of linear DNA molecules
What does the chromosome of Borrelia look like
linear, causative of lyme disease, have hairpin telomeres
How do hairpin telomeres affect Borrelia
Eliminate the end replication problem caused by free ends since the machinery can round the hairpins. Creates a problem that the molecule cannot be partitioned into 2 daughter cells. Uses a process of DNA breakage and refolding to separate out 2 linear molecules with hairpin telomeres
What does telomere resolvase do (ResT)
a specialized DNA breakage and rejoining enzyme that forms hairpin telomeres from replicated intermediates to allow partition of the replicated products to daughter cells.
Describe the linear chromosomes of streptomyces
Linear Streptomyces chromosomes and plasmids are capped at their 5’ ends by a terminal protein that is covalently attached to the 5’ ends of the DNA.
Telomere have a complicated palindromic strucutre and recruits the terminal protein
What is telomerase reverse transcriptase and telomerase RNA
telomerase reverse transcriptase (TERT): the protein component of telomerase.
telomerase RNA (TR): the RNA component of telomerase
What is telomere associated primase (Tap)
a specialized primase in Streptomyces that synthesizes a short DNA primer extended from an active site threonine in the terminal protein
What is a terminal protein
a protein that protects linear chromosome ends in Streptomyces and provides an attachment site for a DNA primer laid down by a specialized primase
