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Lecture7 Notes

Lecture7 Notes - Wed 8.19.09 Lecture 7 DNA Repair I The...

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Wed. 8.19.09 Lecture 7: DNA Repair I. The proofreading function of DNA polymerases during DNA synthesis DNA Damage o DNA damage is unavoidable and arise by spontaneous cleavage of chemical bonds in DNA. This may occur via: Genotoxic chemical in the environment. Certain chemical by-products of normal cellular metabolism Environmental agents such as UV light and ionizing radiation. Copying errors introduced by DNA polymerase during replication. o If the DNA sequence is left uncorrected, cells might accumulate so many mutations that they could no longer function properly and may no longer be viable. o Therefore, the prevention of DNA sequence errors in all cell types is important for survival. Certain DNA polymerases are able to not only add a nucleotide to a new strand, but also to remove a nucleotide if it is a mistake. DNA Polymerases: Oops my bad! o The first line of defense in preventing mutations is DNA polymerase itself. o Occasionally, during DNA replication, DNA polymerase add an incorrect nucleotide is added to the growing 3’ end of the daughter strand. o E. coli DNA polymerase: 1 incorrect nucleotide/ 10^4 polymerized nucleotide. o This remarkable accuracy is due to proofreading by E. coli DNA polymerase III. Proofreading: 3’ to 5’ Exonuclease Activity o Proofreading depends on the 3’ to 5’ exonuclease activity of some DNA polymerases. When an incorrect base is incorporated during DNA synthesis, the polymerase: Pause Transfers the 3’ end of the growing chain to the exonulease site, where , The incorrect mispaired based will be removed. The 3’ end is then transferred back to the polymerase site, where this region is copied correctly. Exonuclease: remove nucleotide from the end.
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