TERMINATION
Termination of DNA replication is less well understood than initiation and elongation. Most commonly, termination occurs when converging replication forks meet. Where the replication forks meet is not usually prespecified. Such midpoint localisation depends on the relative start times and speed of progression of each of the converging replication forks.
When two replication forks converge, topoisomerase (Topo I) runs out of space to act and leaves. The ensuing build up of torsional strain gets transmitted behind the replication forks, and this is dealt with by another topoisomerase - Topo II. The two replisomes pass each other in opposite directions, and it is thought that the CMG complex slides onto the double stranded DNA of the last Okazaki fragment. The last Okazaki fragment is matured and the DNA is ligated and so DNA replication is complete. Finally, Helicase is removed. This starts with the ubiquitination (Pop-up: For details on ubiquitination, see video link in description) of Mcm7 and then Cdc48 comes in and dismantles the replisome.
However, there is a problem - because the chromosomes are linear, DNA replication does not reach the very end of the chromosome, since Okazaki fragments require RNA primers attached ahead of the lagging strand. This results in the loss of DNA with each cycle. Bacteria, with their circular chromosomes, do not have this issue, since their replication terminates only when the two replication forks meet one another at a designated termination site.
Eukaryotic cells address the problem of DNA shortening during replication using telomeres (pop-up), regions of repetitive nucleotide sequences at the ends of chromosomes. In humans, this repetitive sequence is TTAGGG, and it is repeated 100-1000 times in telomere regions. This prevents the chromosome ends from damage, since the only DNA that gets lost is the meaningless telomere DNA. Once the cumulative DNA loss prevents further division, cells can no longer divide - they have reached what is known as the Hayflick limit. In the germ cell line, which passes DNA to the next generation, as well as in some types of stem cells and white blood cells, telomerase prevents degradation from accumulating by extending the repetitive sequence of the telomeres. This does not happen in somatic cells, and so their telomeres shorten with each round of replication. When telomerase mistakenly activates in somatic cells, this can sometimes lead to cancer.
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