| Publication number |
CLPUB00563 |
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| Authors |
Ueda T., Khan S.G., Emmert S., Shahlavi T., Busch D.B., Schneider T.D., Kraemer K.H. |
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| Title |
A G to A change at the splice donor site of intron 2 in the xeroderma pigmentosum group C (XPC) gene alters the efficiency of premRNA splicing. |
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| Citation |
J. Invest. Dermatol. 117:515-515(2001) |
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| Abstract |
We studied the molecular defects in the XPC gene in a 47 y old woman with
XP (XP86BE) with severe sun sensitivity and multiple cutaneous neoplasms.
UV cell killing was 3 times normal in XP86BE skin fibroblasts. Host cell
reactivation of a UV-treated reporter plasmid cotransfected with a vector
expressing wild type XPC message assigned XP86BE to XP complementation
group C. RT-PCR of total RNA revealed two alternatively spliced XPC mRNA
isoforms in the exon 2 region: (I) a deletion of 68 bases at the 3' end of
exon 2 and (II) a 141 base insertion between exons 2 and 3 that retains
the 5' end of intron 2. These changes resulted in frameshifts with new
termination sites that would encode truncated XPC proteins. Genomic DNA
analysis showed a homozygous G to A mutation at the splice donor site of
XPC intron 2. This mutation reduces the information content of splice
donor 2 from 10.2 to +- 2.6 bits and results in use of cryptic donor sites
of 8.6 bits (isoform I) and 9.5 bits (isoform II). The mutation
inactivates a Bsu36 I site in intron 2 that can be used to diagnose the
genomic status of other family members. The splice donor site mutation
identified in XP86BE cells resulted in alternatively spliced XPC mRNA
isoforms which utilize cryptic donors with high information content and
are predicted to encode truncated XPC proteins with defective DNA repair
function resulting in clinical disease.
|
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| Cell lines |
CVCL_M313; XP86BE |
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