DNA REPLICATION

DNA replication.

  DNA is, it's a two-stranded polymer of nucleotides and each strand has a backbone made of

identical sugar and phosphate groups

with different nitrogenous bases pointing inwards, pairing in base

specific manner, A with T and C with G.

 These long molecules are coiled around histones and then supercoiled to give compact chromosomes, each with many

millions of base pairs. All of your genetic material, 23 pairs of chromosomes

to be exact, is present in every single cell in your body. But your cells are

dividing all the time.

Old ones die and new ones are generated to take their place. In fact, apart from

female egg cells, there's not a single cell in your body that was there when

you were born.

So how does each new cell get all of the genetic material? As it happens, all of it

is copied through a process called DNA replication, so that when a cell divide’s

each resulting cell keeps a copy of all of your chromosomes. So how does DNA

replication work? It's an impressive operation, with about a dozen enzymes

working in tandem.

Let's look at a few of these enzymes and see what they do. Helicase is an enzyme

that unwinds the double helix and disrupts the hydrogen bonds between the

bases, thus separating DNA into individual strands and creating a

replication fork. The unwinding of the helix generates strain further ahead in

the chain so as we go

topoisomerase will break, untwist, and reconnect the DNA, always ahead of the

replication fork. With the strands separate we can begin to copy each one,

but the enzyme that copies the strand needs a place to start, so an enzyme

called primase will anneal an RNA primer at a specific location to kick-start the

replication. This primer is about five to ten nucleotides long. Then, another enzyme

called DNA polymerase III binds to the primer and begins to generate a whole new complementary strand, adding nucleotides to the new chain that was initiated by the primer.

 Nucleotides enter the enzymes active site and polymerase catalyzes formation of the phosphodiester bond that joins each new nucleotide as it is added to the complementary strand.

This process will be different for each strand because polymerase will always

add nucleotides to the 3' end of the existing strand, not the 5' end, and the strands are antiparallel so the direction of replication must be in opposite directions for the opposing strands.

On the leading strand, DNA replication moves along with the replication fork

continuously synthesizing the complementary strand and requiring only

the initial primer. But on the lagging strand, polymerase has to go one chunk at

a time as new template is made available. These chunks are called Okazaki

fragments and they are around 100 to 200 nucleotides long. Each one will require

its own primer in order for polymerase to bind and copy the new fragment.

After each fragment is synthesized, DNA polymerase I will go through and replace

the RNA nucleotides from the primer with DNA nucleotides to make sure its DNA all

the way through.

Lastly, because polymerase can't join the last nucleotide of one fragment to the

first nucleotide of another, a separate enzyme called ligase has to go through

and make sure everything is connected.

So, to summarize, helicase unwinds and separates the DNA into two strands.

Primase anneals primers to start things off, and polymerase III copies each strand.

On the leading strand we need just one primer and everything goes continuously.

On the lagging strand we need a primer for each Okazaki fragment.

Then, polymerase I replaces the primers with DNA nucleotides, and ligase seals

everything up. Two identical copies of the original DNA molecule.

This whole process, which is happening in billions of cells in your body at this very moment goes very fast, about 50 base pairs per second.

Moreover, polymerase is very good at getting the code right.

It almost always puts the correct base across from the template strand, and when

it makes a mistake it can usually backtrack and correct it in a process

called proofreading. Even with this, around one in every ten billion base pairs, an error ends up in the final sequence.

Luckily there are enzymes that can recognize these errors and perform

mismatch repair, swapping out the incorrect base for the correct one, just

like other enzymes that repair damage caused by external sources. These enzymes

minimize the possibility of mutation, but as we said, polymerase almost always gets it right. In this way, each strand in the double helix acts as the template for its complement, and we end up with two identical copies of all the genetic material. 

When a cell divides, each new cell retains one of these copies, and when the cell cycle gets to a certain point, these new cells go about copying everything again, to be ready for another division when the time comes.