DNA repair: Dynamic defenders against cancer and aging Page: 4 of 16
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contributions. Identifying genetic variations in the normal population that increase risk of cancer
is of considerable public health interest, and DNA repair genes are likely candidates. Elucidating
the molecular mechanisms that underlie inherited defects in DNA repair will provide a
framework for understanding the complex patterns of predisposing genetic variations that will
surely emerge from large-scale studies of spontaneous human cancers.
Diseases have been linked with defects in all types of DNA repair pathways. For example,
hereditary nonpolyposis colon cancer (HNPCC) results from defects in mismatch repair genes,
and hereditary breast cancer is caused by mutations affecting the breast cancer-associated
proteins BRCA1 or BRCA2 that play a role in DSB repair by homologous recombination. Here
we describe in more detail the devastating human disorders known to be caused by defects in
nucleotide excision repair (Table 1).
Xeroderma pigmentosum (XP). Although rare, XP is the most common of the DNA repair
defective diseases and the most well known. In the United States the frequency of XP is
approximately 1 case per 250,000 and in Japan the frequency is much higher at 1:40,000 .
The discovery of 26 XP children in one small mountain village in Guatemala  focused recent
international attention on XP, but it was first described in 1874  and was first shown to be
caused by defects in NER in the late 1960s . The most evident clinical features of XP are
extreme sun sensitivity with marked thickening of the skin ("xeroderma") together with changes
in pigmentation ("pigmentosum") and a very high incidence of skin cancers on sun-exposed
regions of the body. Eye and neurological abnormalities are also common. XP patients can be
subdivided into eight complementation groups, XP-A through -G plus XP-V, based on which
gene is affected. Seven of the eight genes (XPA through XPG) are directly involved in NER,
while the XPV (variant) gene product is a DNA polymerase that is involved in translesion
synthesis past UV lesions.
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Fuss, Jill O. & Cooper, Priscilla K. DNA repair: Dynamic defenders against cancer and aging, article, April 1, 2006; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc884361/m1/4/: accessed January 20, 2019), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.