DNA polymerase structure and function

 

foreign

polymerization is done Naturally by DNA

and we know that DNA polymerization

process is carried naturally due to the

pyrophosphate that is produced the

hydrolysis of pyrophosphate drives the

reaction forward and we also know that

if there is only one phosphate left any

polymerase cannot seal it

it's called The Nick we need ligase to

add an extra phosphate from ATP and then

cancel the name

now we are going to talk about the

different types of DNA polymerase

different types of DNA polymerase that

are available and in prokaryotic

replication particularly we talk about

different types of polymerases so

here you can see the table in this table

we have DNA polymerase we have three

different types of activities of a DNA

polymerase and ultimately the function

of the DNA polymerase

now a DNA polymerase as I mentioned it

has two kinds of Activity one is the

polymerization

polymerization and the second one is

exonuclease activity or proof reading

right

a proofreading activity

now polymerization direction is

done by all kinds of DNA polymerase

but the exonuclease activity can be of

two different type 5 Prime to three

prime

or

C Prime to five Prime X nucleus activity

but not all the polymer is share same

sort of exonucleus activity different

polymers have different types of

exonuclease activity here we are seeing

five different types of polymerase so

polymer is one

polymerase activity for all the

polymerase are five Prime to three prime

but for polymer is one the exonuclease

activity five to three prime EXO nucleus

activity is present

activity are also present so that means

DNA polymer is one

can go 5 Prime to 3 Prime

polymerization

and it can also

go exonuclease activity

in both Direction

in both the directions

that is a unique feature of DNA

polymerase one unique feature of having

five Prime to three prime exonucleus

activity which is not present in any of

other DNA polymerase

well the rest of the other DNA

polymerase like DNA polymers 2 and 3

they have three prime to five Prime

exonuclease activities

okay

so what are the function of DNA polymer

is one

removes and replaces primers at the end

of DNA replication event due to the

capability of cleaving a DNA strand c25

prime or 5 to 3 Prime they are excellent

choice to utilize them to remove the RNA

or any ribonucleotides from the existing

DNA and fill that Gap

now what is the gap

let's say this is the nearest trend

so these are hydrogen bonds in the

middle

but here are two nucleotides let's say A

and G

no other nucleotide present in the

complementary DNA this region is known

as

a gap

so Gap means

nucleotides are missing Gap means

nucleotida

anything

but a Nick is

when nucleotides are present

only the first four diaster Bond

let me see

this is the difference between a Nick

and a gap

so if there is a gap

what do you need to fill it

nucleotides and polymerase

if there is a Nick then what do we need

to fill it

DNA ligase is needed no nucleotides are

needed and ATP is needed because ligase

requires ATP to function

clear

so the function of polymer is two

polymerase 2 is involved in DNA repair

and

it restarts the replication after damage

DNA Hall synthetic synthesis process

and the polymer is C

is the actual polymerase required for

elongation of the DNA or DNA

replication processing prokaryotes so in

prokaryotic DNA polymerase type DNA

polymerase 3 is the

predominant DNA polymerase for the

process of application

and in prokaryotes polymerase one is

used to fill the gaps

mix never can be sealed by polymerase it

can only be sealed by ligase with ATP

and polymerase 2 is used as a repair

mechanism a polymerase for DNA repair

mechanism

apart from that there are DNA polymers

four and five

four and a four and five both this kind

of DNA polymerase are used very less but

they are mostly used for DNA repair

mechanism

okay and repair mechanism of translation

means if there's a lesion formed in the

DNA lesion means where there is no

proper interaction or pairing of the

nucleotides a soil structure in the DNA

strand those lesions can be removed and

new DNA can be synthesized in that

position by polymerase type 5. but

mainly there are the C Paul 1.2 and Paul

three

the unique feature about DNA polymer is

one is that it carries a 5.3 Prime

exonuclease activity

foreign

foreign

I would like it

so here you'll see the important feature

of DNA polymer is one

you see the DNA polymer is one is a like

it contains two different subunits

so when we treat it with some

proteolytic enzyme

the proteolysis because the protein DNA

polymer is one the proteolysis of

polymerase gives arise to two fragments

one larger fragment and one small

fragment

okay when we do that extracellularly on

the outside of a cell we can do this

outside of the cell

in a environment outside any vitro

process right we add some proteolytic

enzyme it just it degrades of polyvinus

one hollow enzyme Hollow means when the

enzyme is filled with multiple

cellulitis so they separate into two

fragments one large one small the large

fragment is known as cleaner fragment

and the small fragment is basically

having five Prime to three prime

extonuclease activity

now this cleaner fragment contains two

fragments here you can see green and

yellow one with the five Prime to three

prime polymerization activity another

one is another three one into five Prime

exonuclease activity means basically all

the other all two pole three that they

share three to five Prime EXO nucleus

activity which is also being shared by

pole one

so 5 Prime to 3 Prime polymer

polymerization activity C Prime to five

Prime X1 equals activity this is present

in all polymerase one two three

but

the 5 Prime to three prime

exonuclease activity is rare

is found in

only Paul one

and the moment we use the proteolysis we

have these two fragments one large one

small so the large fragment is capable

of carrying out the function of both

five Prime to three prime polymerization

activity 3.5 Prime exonucleus activity

and they rest other the five point three

prime X activity gets separated and this

is not always needed because you know if

you want to delete something or delete

added nucleotide we need to go backward

that is C Prime to five Prime that's why

always the external nucleus activities

are present three to five Prime and not

five to three prime

now we are going to see the examples of

eukaryotic polymerase and look at the

comparison between them

here you can see the eukaryotic

polymerase the polymer is eukaryotes are

named as Alpha Delta Epsilon beta gamma

you can see the Delta and Epsilon are

known as the predominant polymerase is

in eukaryotes they help in elongation of

leading and lagging strength Epsilon

involved with the leading strand Delta

with the lagging strength on the other

hand polymer is Alpha is simply used for

the priming of replication in both the

strands

and polymer is beta involved in DNA

repair polymerase gamma in the

replication of mitochondrial DNA because

Union eukaryotes organelles like

mitochondria have their own DNA and the

mitochondrial DNA

replication is done by polymerase gamma

all right so these are the different

types different DNA polymers is the

classification comparison

now we are going to talk about the DNA

polymerase structure how they look like

this is the DNA polymerase C or policy

structure

basically this is a overall idea of DNA

policy there are different sub uh

assemblies to a ball three structure you

can see it's made with multiple

different subunits

so it looks something like two arms two

hands connected to a body

so consider this as a body known as Tau

unit holding two different mirror

identical sides of the polymerase

together

and the bottom let's say this is the leg

which is built with gamma

Delta Chi

PSI and all these different structures

now these three different portions the

body main bodies the arms made up with

Alpha and this is known as delt Epsilon

Theta and there is beta clamp which will

be loaded here

okay so if you consider this as a

overall structure beta clamp has an

important specific role to play Tau has

a role to hold them together and this

leg which is made with Delta Psi and all

this segment they help to load the beta

note the DNA onto the beta clamp but

beta climb on top of the DNA basically

imagine this is the DNA strand the DNA

strand will be separated

right

once it's separated the polymerase will

load itself

so let's say this is the polymerase

Alpha units Tau connected

okay Alpha m is the body and these are

this is the loader the bitter clamp

will help to load the polymerase

on top of both the template strand

because the DNA replication process that

is going on in the prokaryotes it's

going on in both the strands

both strands simultaneously

both strands simultaneously

so the beta clamp is loaded in both the

strands and the polymerase will move

from five Prime to three prime direction

of newly synthesizing strands Direction

so this was let's say the red one is the

existing parental

C Prime to five Prime

so the New Strand is the blue color 5

Prime to C Prime this is new and

polymerase is movement in this direction

right

so the role of beta clamp is to load the

polymerase

and the alpha units and Tau hold the

structure together

and there is these are known as the

clamp loader and they are also known as

the camp nodal means they load this beta

clamp on top of

the hands you can say the yeah

now Tau the hand means is Epsilon on

this structure so they load it there

this area beta clamp Road so what is the

point of having beta clamp it looks like

a clamp what is the function of a clamp

is to hold something right so there are

two different strands of the DNA here

you can see in this picture and with the

help of the beta clamp

the polymerase is holding

itself on top of the DNA strands so

something like trapezium the trapezoid

that that game you know they have this

uh rulers that hold them into rope for

example two ropes are passing you have

clamp loader with the help of the clamp

loader you're holding in both these

ropes together right

now you'll be moving in the one forward

direction that is 5.3 prime or newly

synthesizing strand without the beta

strand

the polymerase can polymerize but the

rate of polymerization will be very very

low

okay

so what is polymerization rate

number of nucleotides added per minute

or per second that is polymerization

rate

and what is processivity there are two

things one is polymerization

and the second one is

process c v t

what are the difference between the two

polymerization means number of

nucleotides per time per unit time

that is polymerization rate

what is processivity number of

nucleotide added before the fall falls

off

number of nucleotides of polymerase can

attach in one go in one stretch that is

known as the processivity of that DNA

polymerase

the possessivity of DNA polymer 3 is

maximum

that's why DNA polymerase is used as a

primary polymerase for DNA replication

in prokaryotes that is maximum for Delta

in case of okay

so Delta n and the

Epsilon because that's why they are used

for leading and lagging strand

particularly for polymerase it's uh in

broker is Paul three that's working

now without the beta clamp the

processivity drops

polymers can polymerize but let's say 10

off

but with beta clamps loaded with beta

clamps tagged it can polymerize thousand

nucleotides at a time before it falls

off

now the rate of polymerization depends

on the availability of dntps

but processivity is not related to the

availability of dntps

it is also but processivity depends on

both the factors the availability of

dntp as well as the presence of beta

class

okay while polymerization only depends

on

the dntp is the amount of the ntps if

there is no dntp no polymerization in

both the case that's true but in case of

processivity dntp along with dntp beta

clamp

is another important parameter

in this picture you will see a

schematic drawing

of polymerase DNA polymerase 3 a similar

drawing you can see

so you don't need to remember it only

need to know the importance of Tau unit

to hold two identical structures left

and right hand side together as a single

polymerase body

beta clamps are very very important in

order to load the polymerase itself to

the single strands template DN

and what else this gamma and PSI this

structure is a loader of beta clamp the

load beta clamp on top of the strands of

the game

that's all you need to know

okay now one big question comes in

that we know that that this polymerase

you know two different strands are

present in the DNA

this is stand one this is Trend two we

are seeing two different strands and

this strands both are used as a template

strength to synthesize the new Strength

right now let's look at the dilemma here

we have this C Prime to five Prime

existing Strand and we have 5 Prime to

three prime existing strand

so our new Strength synthesis will go

this direction 5 to 3 Prime

and

this is also five to three

this polymerase both are connected

together by Tau

so polymer is at a time can move at Only

One Direction either these or

this

if polymer is moved

right hand side

it's moving five to three prime for this

strand but for this it's opposite

and if polymerase is moving from this 5

Prime to 3 Prime

this is fine but for this trend it's

opposite

if they are not connected by Tau unit

two are separate units they could have

easily polymerized to stand separately

but they are moving in opposite

direction let's assume these are the two

bitter Rings they are moving in opposite

direction but they are connected

together how they move

they should be sharing force and they

should separate

so to prevent that

there is a fold

formation of loop is done

so that concept of DNA looping we'll see

that in a moment so DNA is bent in such

a way that at a time the polymerase will

move only in One Direction of course one

of the Strand will be smoothly

replicated and the Strand with smooth

continuous replication will be known as

leading strand

and the one with breaking small segment

replication at a time will be known as

lagging strand

okay

now this bent is important for the

replication to continue even when the

polymerase are connected the two units

two sides of the polymers are connected

together

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