Base Excision Repair | DNA Repair Mechanism

Summary

This video delves into the base excision repair mechanism, a crucial single-strand DNA repair process. It explains how enzymes like DNA glycosylase, AP endonuclease, DNA polymerase, and ligase work together to identify and fix base damage caused by chemicals or radiation. The video highlights the transformation of cytosine into uracil and the subsequent risk of point mutations during replication. The detailed mechanism showcases the steps from base recognition and removal to the final sealing of the DNA strand, emphasizing the importance of this repair process in maintaining genetic integrity.

Takeaways

• 🧬 The video discusses base excision repair, a mechanism for fixing single-strand DNA damage.
• 🔍 Damage to DNA bases can occur spontaneously due to exposure to chemicals or radiation, often affecting a single base.
• 🧩 The four DNA bases are adenine (A), thymine (T), guanine (G), and cytosine (C), with single base damage leading to mutations.
• 🛠️ Hydrolytic deamination is a common cause of base damage, transforming cytosine into uracil, which is not a normal DNA base.
• 🧬 Base excision repair involves specific enzymes to identify and repair the damaged bases.
• 🔬 DNA glycosylase is the enzyme that recognizes the damaged base and removes it from the DNA strand.
• ✂️ AP endonuclease then cleaves the DNA at the site where the base has been removed, creating a nick in the phosphodiester backbone.
• 🔄 DNA polymerase fills in the missing base, restoring the DNA strand to its original sequence.
• 🔗 DNA ligase seals the nick in the DNA backbone, completing the repair process.
• 📚 Flap endonuclease, such as PEN-1, is involved in long patch base excision repair, dealing with more extensive damage.
• 🔄 The detailed mechanism shows how base excision repair corrects uracil misincorporation during DNA replication, preventing point mutations.

Q & A

What is the main focus of the video?

The video focuses on explaining the base excision repair mechanism, which is a single-strand DNA repair process.

Why is base excision repair important for DNA?

Base excision repair is crucial as it corrects damage to a single DNA strand caused by chemicals or radiation, preventing mutations and maintaining genetic integrity.

What are the common causes of base damage in DNA?

Base damage in DNA is commonly caused by hydrolytic deamination, oxidation, and alkylation, with hydrolytic deamination being the most pronounced.

How does the base damage transform the normal bases in DNA?

Base damage can transform cytosine into uracil, adenine into hypoxanthine, and guanine into xanthine, which are abnormal bases not found in normal DNA.

What is the role of DNA glycosylase in the base excision repair process?

DNA glycosylase recognizes the damaged base and removes it from the DNA strand, initiating the base excision repair process.

What is the function of AP endonuclease in DNA repair?

AP endonuclease recognizes the abasic site (missing base site) and cleaves it, creating a nick in the phosphodiester backbone, allowing for further repair steps.

How does DNA polymerase contribute to the repair process?

DNA polymerase inserts the missing base into the DNA strand after the damaged base has been removed, filling the gap left by the excision.

What is the role of DNA ligase in the final step of base excision repair?

DNA ligase seals the nick in the DNA backbone, completing the repair process and restoring the integrity of the DNA strand.

What is flap endonuclease and when does it act in the repair process?

Flap endonuclease, in the form of PEN-1, removes the flap structure generated during long patch base excision repair when more than one base is synthesized from an abasic site.

How does the presence of uracil in DNA lead to a point mutation during replication?

During replication, if a damaged strand with uracil is used as a template, DNA polymerase will incorrectly pair adenine with uracil instead of cytosine, leading to a change in the genetic code and a point mutation.

Why is it necessary to repair uracil in DNA immediately after it is formed?

Uracil in DNA, if not repaired, will cause errors during replication by leading to incorrect base pairing, which can result in point mutations and genetic disorders.

Outlines

00:00

🧬 DNA Base Excision Repair Mechanism

This paragraph delves into the process of base excision repair, a crucial single-strand DNA repair mechanism that rectifies damage caused by chemicals or radiation. It explains how DNA bases can be altered through hydrolytic deamination, oxidation, and alkylation, leading to the formation of abnormal bases like uracil, hypoxanthine, or xanthine. The paragraph outlines the enzymes involved in this repair process, starting with DNA glycosylase, which recognizes and removes the damaged base, followed by AP endonuclease that cleaves the phosphodiester backbone at the abasic site. DNA polymerase fills in the missing base, and DNA ligase seals the nick. The role of flap endonuclease in long-patch base excision repair is also mentioned. The summary highlights the detailed mechanism, starting from the damage caused by the incorporation of uracil during replication, which can lead to point mutations, to the correction of such errors by the base excision repair pathway.

05:00

👍 Viewer Engagement and Subscription Call

The second paragraph serves as a call to action for viewers, encouraging them to show their appreciation for the video by liking it and giving it a thumbs up. It also reminds viewers to subscribe to the channel for more content, reinforcing the importance of viewer interaction and subscription for the channel's growth and engagement.

Keywords

💡Base Excision Repair

Base Excision Repair (BER) is a DNA repair mechanism that corrects small-scale damage to a single DNA strand. In the video, it is highlighted as the primary process for dealing with base damage caused by chemicals or radiation. BER is crucial for maintaining the integrity of genetic information and preventing mutations that could lead to diseases such as cancer.

💡DNA

DNA, or deoxyribonucleic acid, is the molecule that carries the genetic instructions for the development, functioning, and reproduction of all known living organisms. In the context of the video, DNA is the substrate for the base excision repair process, which is essential for correcting errors that can occur during replication or due to environmental damage.

💡Enzyme

An enzyme is a type of protein that acts as a catalyst to speed up biochemical reactions in the body. In the video, several enzymes are mentioned as key players in the base excision repair process, such as DNA glycosylase and AP endonuclease, which work together to identify and repair damaged DNA bases.

💡Hydrolytic Deamination

Hydrolytic deamination is a chemical reaction where a nitrogen-containing group is removed from a molecule through the action of water. In the video, it is described as a common cause of base damage in DNA, where bases like cytosine can be converted into uracil, leading to the initiation of the base excision repair process.

💡Adenine, Thymine, Guanine, Cytosine (ATGC)

Adenine (A), Thymine (T), Guanine (G), and Cytosine (C) are the four nucleotide bases found in DNA. They pair up to form the rungs of the DNA double helix. The video discusses how damage to these bases can occur and how the base excision repair mechanism addresses such damage to maintain DNA integrity.

💡Uracil

Uracil is a base that is found in RNA but not in DNA. In the video, it is mentioned as a result of hydrolytic deamination of cytosine in DNA, which can lead to replication errors and point mutations if not repaired by the base excision repair mechanism.

💡AP Site

An AP site, or abasic site, is a location in the DNA strand where a base has been removed, leaving a sugar-phosphate backbone with a free phosphate group. The video explains that after DNA glycosylase removes a damaged base, an AP site is created, which is then recognized and acted upon by AP endonuclease.

💡DNA Polymerase

DNA polymerase is an enzyme that synthesizes DNA molecules from deoxyribonucleotide triphosphates. In the context of the video, DNA polymerase is responsible for inserting the correct base to fill the gap created by the removal of a damaged base during the base excision repair process.

💡DNA Ligase

DNA ligase is an enzyme that joins DNA strands together by catalyzing the formation of a phosphodiester bond. In the video, it is mentioned as the enzyme that seals the nick in the DNA strand after the missing base has been inserted by DNA polymerase, completing the repair process.

💡Flap Endonuclease

Flap endonuclease is an enzyme that cleaves specific structures in DNA, such as the flap structure generated during long patch base excision repair. In the video, it is noted that flap endonuclease, in the form of PEN-1, is involved in the repair process when more than one base is synthesized from an AP site.

💡Point Mutation

A point mutation is a type of mutation where one nucleotide in the DNA sequence is changed. In the video, it is explained that if uracil, which is a product of hydrolytic deamination, is not repaired and used as a template during replication, it can lead to a point mutation by pairing with adenine instead of the correct cytosine.

Highlights

The video discusses the base excision repair mechanism for DNA damage, specifically for single-strand DNA repair.

DNA damage can be caused by chemicals or radiation, leading to base modifications such as hydrolytic deamination, oxidation, and alkylation.

Hydrolytic deamination is the most common cause of base damage, transforming cytosine into uracil.

Abnormal bases like uracil, hypoxanthine, and xanthine are not found in normal DNA and can lead to genetic mutations.

Base excision repair is initiated by DNA glycosylase, which recognizes and removes damaged bases.

AP endonuclease recognizes the abasic site and cleaves the phosphodiester backbone.

DNA polymerase inserts the missing base to restore the DNA strand.

Ligase enzyme seals the nick in the DNA strand, completing the repair process.

Flap endonuclease, such as PEN-1, is involved in long patch base excision repair when multiple bases are synthesized.

The video explains the detailed mechanism of base excision repair, starting from DNA damage to the repair process.

Uracil in DNA can cause point mutations during replication if not repaired, as it pairs with adenine instead of guanine.

Uracil DNA glycosylase specifically targets and removes uracil from the DNA molecule, preventing mutations.

The abasic site created by the removal of the damaged base is a critical point for the subsequent steps of repair.

DNA polymerase and DNA ligase work together to fill in the gap and seal the DNA strand.

The video emphasizes the importance of base excision repair in maintaining genetic integrity and preventing mutations.

The process of base excision repair is a crucial single-strand DNA repair mechanism within the cell.

The video concludes with an invitation for viewers to like, subscribe, and support the channel for more informative content.

Transcripts

hello friends in this video we'll be

discussing about the base excision

repair wire damage to DNA is reviewed by

enzyme identity and make sure to note

here that it's a single strand DNA

repair mechanism not a double strand

repair mechanism so here the damage to a

single strand gets repaired we see here

we have a normal DNA molecule present

within the cell and when it gets exposed

to chemicals or additions it

spontaneously damages the bases in a

strand and most of the time we see

single base gets damaged among the four

bases that's ATGC adenine thymine

guanine and cytosine the single base

damage is mediated by hydrolytic

deamination oxidation and alkylation but

hydrolytic domination is more pronounced

order which transforms the bases into

abnormal basis like cytosine adenine and

gowning bases in DNA spontaneously palm

uracil hypo Centene or xanthine

respectively which you will never find

in normal DNA and when this type of

damage is found in the cell the base

excision repair comes into play to

repair the damage now let's have a look

on the enzymes that drive the base

excision repair first of all we have DNA

glycosylase it recognizes the lesion and

remove the damaged base from the strand

then we are AP endonuclease a purine ik

or a pyrimidine and a nucleus depending

upon which base is damaged either it may

be purine or pyrimidine this ap endo

nucleus recognizes the AP side that's a

missing base site and creates sneak in

phosphodiester backbone then we have DNA

polymerase which inserts the missing

base to DNA and finally there ligase

enzyme seals the knee

but we have also another enzyme here

that's called flap endonuclease in the

form of pen one it removes that Phi

prime club generated during long patch

base excision repair

that's when more than one base is being

synthesized from ap site so that time

this flap endonuclease also works in now

let's see the detailed mechanism of base

excision repair when the normal DNA gets

exposed to chemicals and or additions it

damages the DNA and one process is the

hydrolytic termination while the

cytosine base in the Strand changes into

uracil so the chemical damage or the

radiation damage changes this cytosine

based in to uracil now in a DNA molecule

we have uracil instead of cytosine till

now it will not harm the cell or any

process here but during the process of

replication

when this damaged strand having damaged

it base is used as a template strand it

will change the genetic code in the new

DNA the base should be cytosine here and

DNA polymerase will complementary

synthesized gowning but this does not

happen here we have the uracil instead

of cytosine here and for the

complementary base uracil the adenine

will be synthesized it by DNA polymerase

during replication thereby changing the

genetic code and it will cause point

mutation so after having uracil in

strand of DNA it's immediately countered

by the DNA glycosylase that's uracil DNA

glycosylase this and then eliminates

uracil from DNA molecule by cleaving the

N

glycolic bond and initiating the base

excision repair so now we have a DNA

with removed base and the site while

base is missing is termed as ap site

then offer this ap site is recognized it

by AP endonuclease which cleaves the ap

side to yield a three hydroxyl edge

ascent clip

are you deoxyribose phosphate as you can

see in this diagram now wherever why did

DNA strained and this white is to be

filled by the enzyme known as DNA

polymerases and DNA ligase the DNA

polymerase and DNA ligase

finally jumps in wire DNA polymerase

insert the missing base that cytosine

and the NIC is sealed by Danielle I

guess eventually so this is how the base

excision mechanism works in when damage

to DNA is found in the cell in the form

of base damage in single strand I hope

you liked the video if you liked it give

it a thumbs up and make sure subscribe

this channel Thanks