Double strand break products

The formation of J/-H2A.X occurs rapidly after the production of double strand breaks by ionizing radiation with detectable amounts present in seconds and maximal levels reached in about 10 min [57]. y-H2A.X disappears with kinetics consistent with the repair of the double stranded break. Western blots with antibodies that specifically recognize the phosphorylated SQ motif indicate that phosphorylation of this motif occurs in response to double breaks in many organisms, including Drosophila and S. cerevisiae [58]. 

LOMEFLOXACIN t UVA IS min Figure19.3 Useofsupercoiled plasmid circular DNA for detection of ROS production by photo-activated lomefloxacin. Form I supercoiled form (no DNA breaks) form II relaxed form (few DNA single strand breaks) form III linearform (high level of DNA single strand breaks leading to double strand breaks see [38]). 

A discussion of the distribution of stable end products produced by direct ionization in DNA is presented. Single- and double-strand break yields for low LET radiation are discussed. Then work on end products derived from the DNA bases is reviewed. Recent... 

In this double-strand break repair model for recombination, the 3 ends are used to initiate the genetic exchange. Once paired with the complementary strand on the intact homolog, a region of hybrid DNA is created that contains complementary strands from two different parent DNAs (the product of step (2)in Fig. 25-31a). Each of the 3 ends can then act as a primer for DNA replication. The structures thus formed, Holliday intermediates (Fig. 25 31b), are a feature of homologous genetic recombination pathways in all organisms. 

Folkard M, Prise KM, Vojnovic B, Brocklehurst B, Michael BD (2000) Critical energies for ssb and dsb induction in plasmid DNA by vacuum-UV photons an arrangement for irrdiating dry or hydrated DNA with monochromatic photons. Int J Radiat Biol 76 763-771 Folkard M, Prise KM, Turner CJ, Michael BD (2002) The production of single strand and double strand breaks in aqueous solution by vacuum UV photons below 10 eV. Radiat Prot Dosim 99 147-149 FoxRA, Fielden EM, SaporaO (1976) Yield of single-strand breaks in the DNA of E. coli 10 msec after irradiation. Int J Radiat Biol 29 391-394... 

Rashid R, Langfinger D, Wagner R, Schuchmann H-P, von Sonntag C (1999) Bleomycin vs. OH-radi-cal-induced malonaldehydic-product formation in DNA. Int J Radiat Biol 75 110-109 Rothkamm K, Lobrich M (2003) Evidence for the lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Nat Acad Sci USA 100 5057-5082 Sapora O, Fielden EM, LoverockPS (1975) The application of rapid lysis techniques in radiobiology. I. The effect of oxygen and radiosensitizers on DNA strand break production and repair in E. coli B/r. Radiat Res 64 431-442... 

The chnical phenotype of ataxia telangiectasia (AT) syndrome is more striking due to ataxia, cerebral degeneration, and dilated blood vessels in the eyes, but shares many of the characteristics from NBS (chromosome instability, radiation sensitivity, and increased cancer risk). The gene responsible for AT is named ATM and the protein product is a protein kinase, likewise involved in double-strand break repair. 

Figure 18.S.B illustrates a matrix effect during irradiation in air and in an oxygen deficient hypoxic) system. OER, the oxygen enhancement ratio, is the relative dose increase needed to produce the same biological effect in the hypoxic as the oxic case. For X-rays and 7, cell survival increases when oxygen is reduced the addition of oxidants has the opposite effect. This indicates that it is the oxidative radiolysis products of water which are most damaging to the cell. However, no oxygen effect is se for a radiation, thereby supporting the model of double strand breaks by direct hits of the a s.

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