ABSTRACT
Acknowledgments .........................................................................................................................294
References .....................................................................................................................................294
It is nowadays well accepted that damage to the genomic DNA, both from endogenous and
exogenous sources, may have major pathophysiological implications for cells, tissues, and organi-
sms (Hoeijmakers 2001). Depending on its type, its extent, and its persistence, DNA damage may
have various consequences for a cell, as shown in Figure 16.1. Of major importance is that DNA
modifications can lead to mutations, altering the coding sequence of DNA.Mutations may involve a
single gene, a block of genes, or even whole chromosomes. Damage to the DNA may also cause
interference with various normal cellular processes, including DNA replication and DNA transcrip-
tion, and this may result in cell death. To maintain the integrity of the DNA molecule before
initiating DNA replication, transcription, and cell division, cells are provided with several efficient
DNA repair mechanisms (Wood et al. 2001). In some circumstances, these repair processes are
incorrect or incomplete, or otherwise deliberately by-passed (also referred to as damage tolerance).
The process of DNA damage in itself is known to trigger cell cycle arrest, whereby prolongation of
G1 and G2 phases provides additional time for DNA repair prior to DNA synthesis and mitosis,
respectively (Zhou and Elledge 2000). Finally, DNA damage is known to trigger signal
transduction pathways, which promote cellular apoptosis (Figure 16.1).
