Impact of genomic imprinting on genomic instability and radiation-induced mutation.
OBJECTIVE
The purpose of this review is to assess the effect of radiation-induced mutation on genes subject to genomic imprinting, and the consequences of this on the understanding of genomic instability. Genomic imprinting is the phenomenon in which one of the two alleles of a gene is expressed or suppressed depending on the gamete from which it was inherited, thus effectively rendering a cell hemizygous for the expression of certain key genes. The consequence of this is that such loci are potentially more likely targets for mutagenesis since one allele is normally inactive. This is not only important in the recognition of a subgroup of target genes for radiation-induced damage, but also raises the possibility of mutations affecting the epigenotype of key tumour suppressor or tumour promoting genes. Such mutations may in principle affect the stability of imprinting and may fall into a novel class of 'epimutation', where the DNA sequence is not affected, but post-transcriptional mechanisms of epigenotype maintenance are stably altered. These novel mechanisms are discussed in relation with radiation-induced genomic instability and the heritability of tumour predisposition from radiation-exposed parents.


CONCLUSIONS
As yet there is only circumstantial evidence that the targets for radiation-induced DNA and epigenetic damage are imprinted genes, or genes involved in the maintenance of the epigenotype. However, the potential consequences of such genes being important targets for the generation of genomic instability or other forms of damage are serious and could affect the interpretation of the risks of low dose radiation exposure and of epidemiological data.
Schofield
P N
PN
Department of Anatomy, University of Cambridge, UK. PS@mole.bio.cam.ac.uk
D000483:Alleles; D004249:DNA Damage / Q000528:radiation effects; D015870:Gene Expression / Q000235:genetics; D005796:Genes / Q000528:radiation effects*; D018392:Genomic Imprinting / Q000235:genetics*; D009154:Mutation / Q000235:genetics / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D011839:Radiation, Ionizing