Dna repair

the main points of DNA Repair

1. DNA REPAIR BY KANCHITA TEWARI BSC+MSC BIOTECH 8 TH SEM

2. Introduction What does DNA have to do with cancer? Cancer occurs when cells divide in an uncontrolled way, ignoring normal "stop" signals and producing a tumor. This bad behaviour is caused by accumulated mutations, or permanent sequence changes in the cells' DNA . Replication errors and DNA damage are actually happening in the cells of our bodies all the time. In most cases, however, they don’t cause cancer, or even mutations. That’s because they are usually detected and fixed by DNA proofreading and repair mechanisms. Or, if the damage cannot be fixed, the cell will undergo programmed cell death (apoptosis) to avoid passing on the faulty DNA . Mutations happen, and get passed on to daughter cells, only when these mechanisms fail. Cancer, in turn, develops only when multiple mutations in division-related genes accumulate in the same cell.

3. There are mostly 3 ways DNA can be repaired Proofreading Single stranded break repair Double stranded break repair

4. Proofreading DNA polymerases are the enzymes that build DNA in cells. During DNA replication (copying), most DNA polymerases can “check their work” with each base that they add. This process is called proofreading. If the polymerase detects that a wrong (incorrectly paired) nucleotide has been added, it will remove and replace the nucleotide right away, before continuing with DNA synthesis

5. Single – Stranded B reak Repair When only one of the two strands of a double helix has a defect, the other strand can be used as a template to guide the correction of the damaged strand. In order to repair damage to one of the two paired molecules of DNA, there exist a number of excision repair mechanisms that remove the damaged nucleotide and replace it with an undamaged nucleotide complementary to that found in the undamaged DNA strand . TYPES: Base excision repair (BER ) Nucleotide excision repair (NER ) Mismatch repair

6. Base excision repair (BER) Damage to a single nitrogenous base by deploying enzymes called glycosylases . These enzymes remove a single nitrogenous base to create a purin or pyrimidinic site (AP site ). Enzymes called AP endonucleases nick the damaged DNA backbone at the AP site. DNA polymerase then removes the damaged region using its 5’ to 3’ exonuclease activity and correctly synthesizes the new strand using the complementary strand as a template .

7. Nucleotide excision repair (NER) Repairs damaged DNA which commonly consists of bulky, helix-distorting damage, such as pyrimidine dimerization caused by UV light. Damaged regions are removed in 12–24 nucleotide-long strands in a three-step process which consists of 1) recognition of damage, 2) excision of damaged DNA both upstream and downstream of damage by endonucleases, 3) and resynthesis of removed DNA region .

8. Mismatch repair S ystems are present in essentially all cells to correct errors that are not corrected by proofreading. These systems consist of at least two proteins. One detects the mismatch, and the other recruits an endonuclease that cleaves the newly synthesized DNA strand close to the region of damage. In E. coli , the proteins involved are the Mut class proteins . This is followed by removal of damaged region by A n exonuclease , R esynthesize by DNA polymerase, And nick sealing by DNA ligase .

9. Double-stranded break repair Some types of environmental factors, such as high-energy radiation, can cause double-stranded breaks in DNA (splitting a chromosome in two). Double-stranded breaks are dangerous- Because large segments of chromosomes, and the hundreds of genes they contain, may be lost if the break is not repaired. Two pathways involved in the repair of double-stranded DNA breaks are the N on-homologous end joining and H omologous recombination pathways.

10. In non-homologous end joining T he two broken ends of the chromosome are simply glued back together. This repair mechanism is “messy” and typically involves the loss, or sometimes addition, of a few nucleotides at the cut site . So, non-homologous end joining tends to produce a mutation, but this is better than the alternative (loss of an entire chromosome arm )

11. Homologous recombination I nformation from the homologous chromosome that matches the damaged one (or from a sister chromatid, if the DNA has been copied) is used to repair the break. In this process, the two homologous chromosomes come together, and the undamaged region of the homologue or chromatid is used as a template to replace the damaged region of the broken chromosome. Homologous recombination is “cleaner” than non-homologous end joining and does not usually cause mutations

12. KEY POINTS; CONCLUSION Cells have a variety of mechanisms to prevent mutations, or permanent changes in DNA sequence. During DNA synthesis, most DNA polymerases "check their work," fixing the majority of mispaired bases in a process called proofreading. Immediately after DNA synthesis, any remaining mispaired bases can be detected and replaced in a process called mismatch repair. If DNA gets damaged, it can be repaired by various mechanisms, including , excision repair, and double-stranded break repair.

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