DNA ligase and termination of replication
DNA ligase does the final sealing in replication: it closes the nicks (breaks where two neighbouring nucleotides are not yet joined) that remain, so each new DNA strand is continuous.
Remember
DNA polymerase (the enzyme that adds nucleotides to a growing strand) makes new DNA, but only DNA ligase seals the final nicks, so each new strand becomes continuous.
Memory aid
ligase is the "glue" enzyme, and helicase is the "unzipper"
Think of ligase as the glue that joins DNA pieces and helicase as the unzipper that opens the double helix.
In eukaryotic cells, each chromosome has many origins of replication (start points). A replication fork is the Y-shaped point at which the double helix is being opened and copied, and forks move away from the origins until neighbouring forks meet.
Termination is the phase in which forks that started at different origins meet, and the last stretches of DNA are copied.
By then almost all of the new DNA has been made, but it still exists as separate pieces. The leading strand is made in one go, but the lagging strand is made as short pieces called Okazaki fragments, each begun from an RNA primer (a short piece of RNA that lets DNA polymerase start a new fragment).
Once the primers are removed and replaced with DNA, a nick remains between neighbouring pieces, and another where forks meet. DNA polymerase can fill the gap left by a removed primer, yet it cannot join that new DNA to the neighbouring fragment.
DNA ligase seals each nick by forming the missing phosphodiester bond, the link that joins one nucleotide to the next. Nicks between Okazaki fragments and nicks where forks meet are closed in this way, which gives two continuous new DNA molecules (the daughter molecules), each with one original strand and one new strand.
The other enzymes act earlier or do a different job:
- Helicase unwinds the double helix ahead of the fork.
- Primase makes the RNA primers that start each new piece.
- DNA polymerase extends each piece by adding nucleotides.
- Topoisomerase relieves the over-winding of the double helix that builds up ahead of the forks.
Key facts
- Job of DNA ligase
- it seals each nick by forming the missing phosphodiester bond.
- Where it acts
- at the remaining Okazaki fragments and at the points where forks meet.
- Primers first
- the primers are replaced with DNA first, and ligase then seals the nicks that remain.
- Polymerase alone
- it fills the gap left by a removed primer but leaves a nick behind.
- Result
- two continuous daughter molecules, each with one original strand and one new strand.
Exam traps
- Replacing RNA primers with DNA is a real step but not the final one: DNA polymerase fills the gap left by a removed primer yet cannot join that new DNA to the neighbouring fragment, so a nick remains for DNA ligase to seal.
- Topoisomerase deals with twisting strain by cutting and resealing the DNA, which is not the same as closing the nicks between Okazaki fragments, and those nicks are sealed once the primers have been replaced, by a different enzyme.
- RNA primers are temporary: they are removed and replaced with DNA, so primase does not bridge the remaining breaks with RNA left in the finished strand.
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