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.
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!
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.
Let's say you have a small cyst on your arm that needs to be removed. The doctor will be like the excision repair machinery. She will recognize the cyst and cut it out. Of course, she's only going to cut out a small area surrounding the cyst, not your entire arm. Then maybe you'll get stitches to seal up the cut (kind of like DNA ligase), and your body will replace the damaged tissue with fresh new tissue (kind of like DNA polymerase).
But isn't it great when we don't have to cut out parts of our body? Maybe cells feel that way about the next type of repair, direct repair. In direct repair, damaged bases are directly repaired without removing any parts of the DNA. Cool! How does it work?
One example of direct repair is photoreactivation. Maybe you remember that UV irradiation, or exposure to UV light, can cause neighboring pyrimidines, like T and C, to covalently bond to each other. This is not normal and causes a bump in the DNA backbone that will stop DNA replication. Uh oh. So something has to be done.
In photoreactivation, an enzyme called DNA photolyase uses energy from light to break the bonds between the cross-linked bases. Simple as that! Now the bases are back to normal, and nobody had to be cut out and replaced! It's also very convenient that DNA photolyase uses energy from light to do its job, because usually it's sunlight that causes the problem in the first place!
In today's lesson, we've learned about three ways that cells can repair DNA damage. We defined DNA damage as situations when nucleotide structures are changed or the DNA strands are broken. The mechanisms we learned about today are for replacing damaged nucleotides.
First, in base excision repair, a single damaged base is recognized and removed. It's important to remember that only the base is removed, not the whole nucleotide. Once the base is removed, a nick is made in the DNA backbone near the damaged site. DNA polymerase comes in and replaces several nucleotides in the area, and DNA ligase seals up the gaps.
The second method we learned was nucleotide excision repair. In this one, the repair machinery recognizes and repairs large, bulky areas of DNA damage. Two single-strand cuts are made and the damaged portion is released and degraded. Then DNA polymerase comes in to replace the segment that was cut out, and DNA ligase seals the nicks.
The last method we learned was direct repair, where damaged bases are directly repaired without removing any parts of the DNA. We can understand why our cells would want to avoid surgery on their DNA whenever possible, right? The example we learned was photoreactivation, where an enzyme called photolyase uses energy from light to repair cross-linked bases caused by UV irradiation.
Complete this video lesson, then exhibit your ability to:
- Recall the meaning of DNA damage
- Detail the ways in which mutations occur
- Describe the correlation between base excision repair and polymerase
- Explain how bulky DNA is fixed with nucleotide excision repair
- Understand how direct repair works without removing any DNA