DNA damage detection

It's estimated that the DNA of a mammalian cell is severely damaged several thousand times per day. In order to preserve the integrity of the genome, cells need to be able to accurately and rapidly detect when damage has occurred. How this is achieved is currently unknown.

Left unrepaired, the myriad types of damage that can occur in genomic DNA pose a serious threat to the faithful transmission of the correct complement of genetic material. Defects in DNA damage signaling and repair result in genomic instability, a hallmark of cancer, and often cause lethality, underlining the importance of these processes in the cell and whole organism. The past decade has seen huge advances in our understanding of how the signal transduction pathways triggered by DNA damage radically alter cell behavior. In contrast, it is still unclear how primary DNA damage is detected and how this interfaces with signal transduction and DNA repair proteins."

Source : Science, 297, 547 ^{[ paywalled ]}

DNA can be damaged in multiple ways, cell infection, radiation, chemical reaction, heat &etc., possibly causing severe local problems for the organism concerned (e.g. cancer etc.) and, if replicated, can permanently damage the genome, and so the prospects for future generations.

Damage detection is therefore a crucial and demanding 24hr requirement for any organism.

Determining the precise structures with which DNA repair and signaling proteins interact at sites of DNA damage and analyzing how these structures are created represent critical issues and it is likely that a combination of experimental approaches - biochemical, structural, and genetic - will be required to address these problems. The question of how lesion-specific repair factors are initially directed to DNA lesions also represents a major challenge for future research."

[ source as above ]

Editor's note : The DNA 'code' shares some similarities with a computer program in that the consequences of damage to any particular region varies enormously. Some parts can be changed with very minimal consequences, and others will cause catastrophic damage.

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