13.2: Erreurs de copies du génome

DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.

1. Proofreading – DNA polymerase enzymes, for example, introduce 1 incorrect nucleotide per 100,000 bases. These errors are detected and rectified during the DNA replication itself by DNA polymerase enzymes. These enzymes possess 3'→5' exonuclease activity that excises the incorrect base from the daughter strand and replaces it with the correct nucleotide.
2. Mismatch repair – DNA repair enzymes repair the wrong bases or point mutations in the DNA post replication but before mitosis.
3. DNA damage repair pathways – DNA is also prone to physical or chemical damage caused by mutagens. DNA damage repair mechanisms operate throughout the cell cycle and can repair point mutations and large-scale genome rearrangements. If the DNA damage is severe, the repair pathway will block cell cycle progression and initiate apoptosis.

In addition to errors during DNA replication, mutations can also be caused by mobile genetic elements called transposons. They are small DNA repeat elements that can jump from one place to another on the DNA strand and disrupt the gene functions at their site of insertion. They can also cause inversions, gene duplication, or create novel genes. Transposons are of two major types:   DNA transposons, which transpose directly as DNA, and  RNA or retrotransposons, which transpose via an RNA intermediate. Some of these transposons result in target site duplication during their insertion at the new site on the chromosome. Such duplications at the target site can result in gene duplication, which may harm  the cell function.