Types of DNA Repair

From The School of Biomedical Sciences Wiki
Jump to: navigation, search

DNA can be damaged by a variety of sources. Depending on the type of damage DNA can be altered in different ways, the body has ways to repair this damage preventing catastrophic changes to our DNA which would result in a variety of problems.

Contents

Mismatch Repair

As DNA is produced occasionally an error occurs during replication which results in a mismatch base pair (e.g. AG, CT), usually these are corrected almost immediately but occasionally they slip through. To ensure that this does not create problems mismatch repair takes place: an enzyme cleaves the DNA at two sections around the mismatched pair, the section is removed, DNA polymerase then uses the template strand to add new nucleotides[1]. Problems can occur however when which strand is cleaved is chosen at random, then it results in the mutant strand being used as a template for repair. There is, however, a system to prevent this in the replication of DNA. The original strand (being older) is fully methylated however the daughter strand (being younger) is not methylated, the system recognises the level of methylation in each strand and cleaves the less methylated strand preventing incorrect repair

Base Excision Repair

This is the immediate repair being referred to in the previous segment. Usually, there are a number of cells which contain enzymes recognise incorrect base pairing, these enzymes move along the DNA and bind when they detect an incorrect base pairing. Through many different mechanisms the enzyme intrudes on the DNA strand causing a compression which flicks the incorrect base out of the DNA molecule leaving behind a Deoxyribose sugar[2].

AP Repair

This is simply the addition of a base to the deoxyribose sugar implanted into the DNA segment in Base Excision repair. What occurs is the sugar is removed by an AP endonuclease creating a gap, this gap is then filled using DNA polymerase, finally the remaining nick is repaired by DNA ligase[3].

Double-Strand Gap Rpair

Double-strand gaps are caused by a variety of factors but amount to the same thing, a gap in the two strands of DNA which make up the molecule. The resultant gaps usually have 3’ overhangs as nucleases within a cell generally trim them back. The strand is stabilised by ssDNA binding proteins, these proteins displace homologous areas of the template strand in sister chromatids and other chromosomes. The displaced area joins to the 3’ and 5’ end of the broken template strand allowing repair and synthesis in the daughter strand via DNA polymerase[4].

SOS repair system

This is a system in which replication of a damaged segment of DNA can take place across mutations in the DNA, however, the resultant strand is very prone to error meaning it is unlikely to be a faithful replica of the original strand. It is not always active but rather is activated by the detection of DNA damage. What actually occurs is the growing replication for goes across the damaged strand adding nucleotides at random as it cannot use the original strand as a template[5].

Nucleotide Excision Repair

This is when a stretch of damaged DNA is excised from the duplex. What occurs is that any damage to the DNA strand can act as a substrate for enzymes used in repair, to this effect the distortion recruits normal transcriptional factors to unwind the DNA, this then allows repair endonucleases to make cuts several nucleotides away from the mutated segment; the mutated segment is then broken down; DNA polymerase adds nucleotides to the 3’ hydroxal group – resynthesizing the segment using the unmutated strand as a template - and finally DNA ligase joins the remaining nicks together[6].

References

  1. L Hartel, M Ruvalo , Chapter 14 Mechanisms of DNA repair in: Molecular mechanisms of Mutation and DNA Repair, pg 551-555 ,genetics: analysis of genes and genomes 8th ed, 5 wall street Burlington, 2012, Jones and Bartlett
  2. L Hartel, M Ruvalo , Chapter 14 Mechanisms of DNA repair in: Molecular mechanisms of Mutation and DNA Repair, pg 551-555 ,genetics: analysis of genes and genomes 8th ed, 5 wall street Burlington, 2012, Jones and Bartlett
  3. L Hartel, M Ruvalo , Chapter 14 Mechanisms of DNA repair in: Molecular mechanisms of Mutation and DNA Repair, pg 551-555 ,genetics: analysis of genes and genomes 8th ed, 5 wall street Burlington, 2012, Jones and Bartlett
  4. L Hartel, M Ruvalo , Chapter 14 Mechanisms of DNA repair in: Molecular mechanisms of Mutation and DNA Repair, pg 551-555 ,genetics: analysis of genes and genomes 8th ed, 5 wall street Burlington, 2012, Jones and Bartlett
  5. L Hartel, M Ruvalo , Chapter 14 Mechanisms of DNA repair in: Molecular mechanisms of Mutation and DNA Repair, pg 551-555 ,genetics: analysis of genes and genomes 8th ed, 5 wall street Burlington, 2012, Jones and Bartlett
  6. L Hartel, M Ruvalo, Chapter 14 Mechanisms of DNA repair in: Mollecular mechanisms of Mutation and DNA Repair, pg 551-555 , genetics: analysis of genes and genomes 8th ed, 5 wall street Burlington, 2012, Jones and Bartlett
Personal tools
Namespaces
Variants
Actions
Navigation
Toolbox