DNA Repair Mechanisms PDF

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Document Details

CommendableSard7063

Uploaded by CommendableSard7063

Loyola College

Tags

DNA repair genetics molecular biology biology

Summary

This document provides an overview of DNA repair mechanisms, specifically focusing on photoreactivation and excision repair. It illustrates the process of thymine dimer formation and subsequent repair processes. The document includes diagrams and visual aids to explain the concepts effectively.

Full Transcript

**(a)** * HN * N * O * N **(b)** * H<sub>2</sub>O + → H + OH<sup>.</sup> *thymine dimer* **(b)** * H<sub>2</sub>O + → H + OH<sup>.</sup> *hydroxyl radical* ## Pyrimidine Dimer ### Ultraviolet light * T * T * T * T * Kink * ### Thymine dimer * T * A * T * A * T ## UV light **Dama...

**(a)** * HN * N * O * N **(b)** * H<sub>2</sub>O + → H + OH<sup>.</sup> *thymine dimer* **(b)** * H<sub>2</sub>O + → H + OH<sup>.</sup> *hydroxyl radical* ## Pyrimidine Dimer ### Ultraviolet light * T * T * T * T * Kink * ### Thymine dimer * T * A * T * A * T ## UV light **Damage Recognized:** * thymine dimer * 5'- A G T A T T C T G A -3' * 3'- T C A T A A G A C T -5' **Nucleotide Excision Repair:** * Nuclease cuts strand * 5'-A G T A T T C T G A -3' * 3'-T C A T A A G A C T -5' * Helicase removes damaged section * 5'-A G T A C T G A -3' * 3'-T C A T A A G A C T -5' * DNA pol I and DNA ligase make repairs * 5'-A G T A T T C T G A -3' * 3'-T C A T A A G A C T -5' **Photoreactivation:** * photolyase binds * 5'- A G T A T T C T G A -3' * 3'- T C A T A A G A C T -5' * visible light * 5'-A G T A T T C T G A -3' * 3'-T C A T A A G A C T -5' * thymine dimer bond broken * 5'-A G T A T T C T G A -3' * 3'-T C A T A A G A C T -5' **(a)** **(b)** ## (a) Photoreactivation repair * T A T * A A * Dimer repaired * T T * A A * Normal pairing restored * T T * A A * Dimer forms * T A T * A A * Excision of dimer * T A T * A A * uvr gene products * T T * A A ## (b) Excision repair * T A T * A A * DNA polymerase I fills in gap. * T T * T T * 5' * 3' * A A * Normal pairing restored * T T * A A * DNA ligase seals gap * T T * A A ## Visible light * 3' - - - - - - - - T - - - - - - - 5' * 5' - - - - - - - - T - - - - - - - 3' * Thymine dimer * 3' - - - - - - - - T T - - - - - - - 5' * 5' - - - - - - - - T T - - - - - - - 3' * Photolyase * 3' - - - - - - T T - - - - - - - 5' * 5' - - - - - - T T - - - - - - - 3' * Cleavage of cyclobutanering * 3' - - - - - - - - T - - - - - - - 5' * 5' - - - - - - - - T - - - - - - - 3' * Damage repaired * 3' - - - - - - - - - - - - - - - - 5' * 5' - - - - - - - - - - - - - - - - 3' * Photolyase released ## Fig 9.17: Photoreactivation for repair of thymine dimer **(a)** * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * UV irradiation * Thymine dimer * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(b)** * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Binding of photoreactivating enzyme to thymine dimer * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Enzyme * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Absorption of blue light **(c)** * Light - activated enzyme * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(d)** * Release of enzyme * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(e)** * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ## Cleavage of thymine dimer crosslinks by photoreactivation. **(a)** Segment of DNA containing adjacent thymine bases. **(b)** Thymine dimer formation as a result of UV irradiation. **(c)** Binding of the photoreactivating enzyme to the thymine dimer-containing segment of the DNA molecule. **(d)** Cleavage of the dimer crosslinks by the photoreactivating enzyme using energy from the absorption of blue light. **(e)** Release of the photoreactivating enzyme, leaving a repaired, structurally normal DNA molecule. The arrows indicate the opposite polarity of the complementary strands。 **(a)** * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * UV irradiation * Thymine dimer * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(b)** * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Single-strand cleavage * Endonuclease * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(c)** * Exonuclease * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(d)** * DNA polymerase * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Newly synthesized DNA **(e)** * DNA ligase * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(f)** * A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ## Diagram of the excision repair pathway for the removal of thymine dimer from DNA. **(a)** Segment of DNA containing two adjacent thymine bases. **(b)** Thymine dimer formation as a result of UV irradiation. **(c)** An endonuclease-induced single-strand cut adjacent to the thymine dimer. **(d)** An exonuclease-catalyzed removal of six nucleotides, including the thymine dimer. **(e)** Resynthesis of the excised segment by a DNA polymerase. **(f)** Formation of the final phosphodiester bond by DNA ligase. The arrows indicate the opposite polarity of the two complementary strands. **(a)** * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Wild-type * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Thymine dimer * Irradiation * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(b)** * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Semiconservative replication * Thymine dimer * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(c)** * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Recombination * " Sister" Chromosomes * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **(d)** * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Nonviable? * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * Wild-type * A - - - - - - - - - - - T - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ## Simplified version of postreplication recombination repair of UV-induced damage in DNA. **(a)** Segment of a DNA molecule containing adjacent thymine bases. **(b)** Formation of thymine dimers during UV irradiation. **(c)** Replication of dimer-containing DNA. Gaps are present in the nascent strands (gray) because of the inability of the distorted dimer-containing regions of the parental strands to function as templates for DNA polymerases. After a lag period, synthesis is reinitiated past the dimers, leaving the indicated gaps. **(d)** Recombination between the "sister chromosomes," producing one undamaged DNA molecule and one doubly damaged DNA molecule. The net effect is the production of one undamaged chromosome from two damaged ones or, quite possibly, one viable product from two inviable ones. Details of the recombination process have been purposely omitted since they are not yet clear. Nucleases, a DNA polymerase, and DNA ligase are undoubtedly involved. ## Figure 8-7: SOS repair * A DNA molecule in an early stage of replication is irradiated with ultraviolet light and thymine dimers are formed. * The SOS system is induced and all subsequent replication (shown in red) has a higher-than-usual number of misincorporated bases (red dots). * Some of these bases can be removed by the mismatch repair system. * Irradiation, formation of dimers * Induction of SOS system; error-prone replication (red) bypasses dimers

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