Chapter 8-1. DNA Correction and Repair
Recommended Reading: 【Biology】 Chapter 8. Central Dogma
1. Mutagens
3. Correction
4. Repair
5. Failure of DNA Correction and Repair
1. Mutagens
2. Original Mark
⑴ Methylates the A base of the template strand to mark it as the original.
⑵ Dna methylase is involved.
⑶ Methylates the 5’-GATC-3’ sequence in the ori C region.
3. Correction
⑴ DNA polymerase has correction functions, and the replication error rate is 1/107.
⑵ Mechanism 1. Exonuclease
⑶ Mechanism 2. 3’ → 5’ correction (DNA pol I, II, III): The 3’ → 5’ exonuclease activity allows correction of errors that occur during DNA synthesis.
⑷ Mechanism 3. 5’ → 3’ correction (DNA pol I): 5’ → 3’ exonuclease activity
4. Repair
⑴ If repair enzymes correct errors, the replication error rate is 1/109.
⑵ Type 1. Dimer recovery
Figure 1. Dimer recovery mechanism
① 1st. Ultraviolet light induces pyrimidine dimers (TT) between adjacent thymines.
② 2nd. DNA photolyase recognizes changes in the phosphodiester backbone and binds to the pyrimidine dimer.
③ 3rd. DNA photolyase absorbs blue light (visible light over 300 nm) and becomes activated.
④ 4th. The activated DNA photolyase separates thymine from the DNA.
⑶ Type 2. Excision Repair
① Overview
○ The most common repair system capable of fixing various structural damages in DNA.
○ Best characterized in E. coli, with various modified repair mechanisms present in other organisms.
② Type 2-1. Mismatch excision repair
○ Characteristics: Uses original marks, Mut proteins, and DNA pol III.
Figure 2. Excision repair process in E. coli
③ Type 2-2. Base excision repair
○ Definition: A repair method for cases where bases are damaged by oxidation, alkylation, hydrolysis, or deamination, forming U bases.
○ Process 1. DNA glycosylase cleaves between the damaged base and the pentose sugar, removing only the base.
○ Process 2. AP endonuclease cleaves the sugar-phosphate backbone at the 5’ side of the AP site where only the base has been removed.
○ AP: apurine or apyrimidine
○ Process 3. AP lyase, endonuclease, phosphodiesterase: Remove the remaining parts of the damaged nucleotide.
○ Process 4. DNA polymerase: Synthesizes nucleotides in the removed region.
○ In E. coli, DNA pol I is involved, while in mammals, DNA pol β is involved.
○ Process 5. DNA ligase: Seals the nick.
④ Type 2-3. Nucleotide excision repair
○ Definition: A repair process for large, helix-distorting damages such as pyrimidine dimers.
○ Process 1. Incision step
○ Step 1-1. Repair endonuclease: Recognizes and cleaves the distorted region caused by thymine dimers.
○ Step 1-2. Cuts the sugar-phosphate bond 8 nucleotides upstream of the thymine dimer on the 5’ side.
○ Step 1-3. Cleaves the sugar-phosphate bond 4–5 nucleotides downstream of the thymine dimer on the 3’ side.
○ Ultimately, two cuts are made 12–13 nucleotides apart.
○ Helicase and exonuclease are involved in steps 1-2 and 1-3.
○ Process 2. DNA polymerase I (pol I) binds to the 3’-OH group at the end of the cut site.
○ Step 2-1. Removes the DNA fragment containing the thymine dimer while synthesizing a new strand.
○ Step 2-2. In eukaryotes, DNA pol ε/δ is involved.
○ Process 3. Ligase seals the newly synthesized fragment into the original DNA strand.
⑷ Type 3. High-fidelity post-replication repair: Increased Lex A protein → Increased accuracy
⑸ Type 4. SOS repair: Emergency repair mechanism. Decreased Lex A protein → Increased Rec A protein activity → Decreased accuracy
5. Failure of DNA Correction and Repair
⑴ Leads to frequent mutations.
Input: 2019.03.03 00:37