Damage amplification reaction

Damage Amplification Reaction of DNA Radical Intermediates with Proximal DNA Bases and Sugars... 

Mechanistically, this damage amplification reaction is not yet understood. Obviously, a second dAdo molecule is required for the reaction to proceed. When the termination of the radicals becomes very fast, this reaction no longer can proceed efficiently. As a consequence, the yields of 5, 8-cyclo-dAdo and 5 -CHO-dAdo drop dramatically at very high dose rate, i.e., under the conditions of pulse radiolysis (Fig. 10.1, triangles Wagner et al. 1999). This is one of the reasons, why this reaction cannot be studied with this technique. 

This type of damage amplification reaction is also observed in polynucleotides and in DNA (Chaps 11.2 and 12.5). 

Clustered Lesions and Damage Amplification Reactions (Tandem Lesions) 391... 

Another damage amplification reaction has been observed with a dinucleotide model which allowed to generate a Thy-5-yl radical specifically. In the presence of 02, it causes the formation of the 2-dRL lesion at the adjacent nucleotide unit (Chap. 10.3). Based on this, -OH-addition to C(6) of T and C could give rise to this tandem lesion also in DNA (as yet not detected). 

It has thus been concluded that the chemical repair, that is in competition with a reaction of the DNA radicals with Oj, may reduce the severity of DNA damage by preventing damage amplification reactions induced by peroxyl radicals (see below). 

The polymerase chain reaction (PCR) is an ideal tool for the study of ancient DNA because it has the ability to amplify a small number of intact DNA molecules that exist in a complex mixture of large amounts of partially degraded and modified templates. Of crucial importance for the use of ancient DNA extracts is the extent to which the damage limits or inhibits the enzymatic reaction. An observation often made is that the maximum sizes of amplifiable products are reduced in old, damaged DNA compared to modem DNA extracts.14 This is also true for DNA from ancient bones, which seem in many cases to allow for longer amplifications than soft tissues. For example, we have determined the maximum size of amplifiable DNA from 3500-year-old moas found at a dry cave site in New Zealand and found that, whereas soft tissues allowed the amplification of pieces only up to 120 bp, bone extracts from the same individual yielded products of up to 380 bp. However, DNA extracted from a modem ratite bird easily allowed the amplification of pieces of over 1000 bp.15... 

If the damaged strand is carried over into a new reaction vessel, it is prevented from functioning as a template for amplification. Effective sterilization requires the use of these reagents at concentrations that are tailored to the length and sequence of the target and the level of amplification (Table 3). 

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