Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 43, Pages 15410-15415Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0404587101
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UV-sensitive syndrome ((UVS)-S-s) is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. (UVS)-S-s cells show IJV hypersensitivity and defective transcription-coupled DNA repair of UV damage. It was suggested that (UVS)-S-s does not belong to any complementation groups of known photosensitive disorders such as xeroderma pigmentosum and Cockayne syndrome (CS). To identify the gene responsible for (UVS)-S-s, we performed a microcell-mediated chromosome transfer based on the functional complementation of UV hypersensitivity. We found that one of the (UVS)-S-s cell lines, UV(s)1KO, acquired UV resistance when human chromosome 10 was transferred. Because the gene responsible for CS group B (CSB), which involves neurological abnormalities and photosensitivity as well as a defect in transcription-coupled DNA repair of UV damage, is located on chromosome 10, we sequenced the CSB gene from UV(s)1KO and detected a homozygous null mutation. Our results indicate that previous complementation analysis of UV(s)1KO was erroneous. This finding was surprising because a null mutation of the CSB gene would be expected to result in CS features such as severe developmental and neurological abnormalities. On the other hand, no mutation in the CSB cDNA and a normal amount of CSB protein was detected in Kps3, a (UVS)-S-s cell line obtained from an unrelated patient, indicating genetic heterogeneity in (UVS)-S-s. Possible explanations for the discrepancy in the genotype-phenotype relationship in UV(s)1KO are presented.
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