DNA Damage Response and Repair: Insights into Strategies for Radiation Sensitization [chapter]

Joshua D., Kristopher T., Kimberly Ng, Bob Carter, Santosh Kesari, Clark C.
2011 Selected Topics in DNA Repair  
DNA repair and damage response following ionizing radiation While Ionizing Radiation (IR) has been shown to induce a plethora of cellular effects, it is widely held that its tumoricidal activity is largely related its effect on DNA 13 . IR induces multiple types of DNA lesions, including damages to the nucleobase, sugar, and phosphate back bone 13 . Ultimately, these lesions, if unrepaired, are converted into Double Stranded DNA Breaks (DSBs). DSBs are highly cytotoxic as the presence of a
more » ... presence of a single DSB in a cell is sufficient to induce death [14] [15] [16] [17] [18] [19] . Our understanding of DNA damage response and DSB repair has expanded exponentially in the past decade. To make this vast information more accessible to the reader, we will organize the information into the following sections: 1) general mechanism of DSB repair, 2) mechanism by which DNA damage response activates DSB repair, and 3) effect of DNA damage on cell cycle progression. General mechanism of DSB repair DSBs are repaired by two major mechanisms: Non-Homologous End Joining (NHEJ) or Homologous Recombination (HR) 20, 21 . The simplest way of repairing DSB is by re-ligation. This process is termed NHEJ since no significant DNA sequence homology at the broken ends is required. Instead, the NHEJ enzymatic machinery relies on limited processing of the DNA ends followed by annealing short stretches of complementary DNA sequences.
doi:10.5772/25216 fatcat:2db4mhdgpndtzlwibtbizl4bgq