The maintenance of genome integrity and fidelity is essential for the proper function and survival of all organisms. This task is particularly daunting due to constant assault on the DNA by genotoxic agents (both endogenous and exogenous), nucleotide misincorporation during DNA replication, and the intrinsic biochemical instability of the DNA itself.
Failure to repair DNA lesions may result in blockages of transcription and replication, mutagenesis, and/or cellular cytotoxicity.In humans, DNA damage has been shown to be involved in a variety of genetically inherited disorders, in aging,and in carcinogenesis.
All eukaryotic cells have evolved a multifaceted response to counteract the potentially deleterious effects of DNA damage Upon sensing DNA damage or stalls in replication, cell cycle checkpoints are activated to arrest cell cycle progression to allow time for repair before the damage is passed on to daughter cells. In addition to checkpoint activation, the DNA damage response leads to induction of transcriptional programs, enhancement of DNA repair pathways, and when the level of damage is severe, to initiation of apoptosis.All of these processes are carefully coordinated so that the genetic material is faithfully maintained, duplicated, and segregated within the cell.
Failure to repair DNA lesions may result in blockages of transcription and replication, mutagenesis, and/or cellular cytotoxicity.In humans, DNA damage has been shown to be involved in a variety of genetically inherited disorders, in aging,and in carcinogenesis.
All eukaryotic cells have evolved a multifaceted response to counteract the potentially deleterious effects of DNA damage Upon sensing DNA damage or stalls in replication, cell cycle checkpoints are activated to arrest cell cycle progression to allow time for repair before the damage is passed on to daughter cells. In addition to checkpoint activation, the DNA damage response leads to induction of transcriptional programs, enhancement of DNA repair pathways, and when the level of damage is severe, to initiation of apoptosis.All of these processes are carefully coordinated so that the genetic material is faithfully maintained, duplicated, and segregated within the cell.
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