Reversing DNA Damage Caused by Mutagens and Irradiation

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  • 0:01 DNA Damage
  • 1:15 Base Excision Repair
  • 3:06 Nucleotide Excision Repair
  • 4:03 Direct Repair
  • 5:41 Lesson Summary
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Lesson Transcript
Instructor: Katy Metzler

Katy teaches biology at the college level and did her Ph.D. work on infectious diseases and immunology.

Nobody likes to have surgery, but sometimes it's necessary to cut out the bad parts and replace them with fresh new tissue. The same is true for DNA! In this lesson, learn how DNA damage can be repaired in both surgical and non-surgical ways.

DNA Damage

As you've learned, mutations, or changes in DNA sequences, can wreak havoc on cells. They can lead to nonfunctional proteins, producing proteins at the wrong times, and cancer among other major issues. Unfortunately, no real mutations are known to give organisms superpowers no matter what the comic books say. Too bad.

Anyway, do you remember how mutations can happen? One way is that cells can make mistakes, kind of like typos, while they are replicating their DNA. Two other ways that we've learned about in this chapter are irradiation and chemical mutagens. Irradiation and mutagens don't only cause mutations, they also damage DNA. What do I mean by damaging DNA?

DNA damage is when the nucleotide structures are changed or the DNA strands are broken. It's not just that the wrong nucleotide is put into the sequence; it's really that physical damage is done to nucleotides or the DNA backbone.

You know by now that cells are pretty amazing, so how do they deal with DNA damage? They must have a way. Actually, they have several methods that they can use depending on what kind of damage has occurred. In this lesson, we'll learn about how cells can repair DNA damage that is done to one strand of the DNA.

Base Excision Repair

The first DNA repair method we'll talk about is base excision repair. This type of repair is the most common way for cells to repair damaged nucleotide bases in DNA. Recall that nucleotides are not the same thing as bases. In this diagram of a nucleotide, the base is shown here. The bases are what bond together in pairs, allowing the two DNA strands to stick together.

Often times, chemical mutagens actually change the chemical structure of bases in the DNA. When their structure is changed, the bases will not pair correctly, which leads to mutations. Luckily, cells can use base excision repair to remove and replace damaged bases.

The first step in base excision repair is for the damaged base to be recognized. This is done by an enzyme called DNA glycosylase. DNA glycosylase recognizes a single damaged base and removes it from the DNA.

There are different kinds of DNA glycosylases that all recognize specific kinds of damaged bases. Importantly, only the base is removed, not the whole nucleotide. That's why this kind of repair is called base excision repair. Excision sounds like scissors and means 'cutting out.' Makes sense!

But now there's a spot in the DNA that still has a backbone, but the base is missing! This is called an apurinic or apyrimidinic (AP) site, depending on whether the missing base was a purine or a pyrimidine. Good thing you can just say AP site, huh? And what happens next is that an enzyme called AP endonuclease recognizes the AP site and makes a small nick in the strand of DNA.

Now our old friend DNA polymerase can come in and replace about one to 10 nucleotides, just to be sure. And DNA ligase, another familiar enzyme to us, will seal the nick in the DNA strand. All better!

Nucleotide Excision Repair

The next type of repair is nucleotide excision repair. As you can tell from its name, in this kind of repair, whole nucleotides are removed and replaced. In nucleotide excision repair, large, bulky areas of DNA damage, possibly with more than one damaged base, can be repaired.

How it works is that first, a damaged piece of DNA is recognized by the nucleotide excision repair machinery. The damaged region is recognized by its general bulkiness, not by specific damaged bases like in base excision repair.

The nucleotide excision repair machinery knows that whole section has got to go, so it makes two single-strand cuts, one on either side of the damaged area, releasing a short section of single-stranded, damaged DNA. Perfect! Now, just like in base excision repair, the DNA polymerase comes in and adds in fresh new nucleotides, and DNA ligase seals the nicks. Good as new!

Direct Repair

The two types of repair we've talked about so far have both been examples of excision repair, where damaged areas are cut out and replaced. To me, excision repair is kind of like minor surgery.

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