A functional analysis of G23A polymorphism and the alternative splicing in the expression of the XPA gene

被引：4

作者：

Butkiewicz, Dorota ^{[1
,3
]}

Krzesniak, Malgorzata ^{[1
,3
]}

Vaitiekunaite, Rasa ^{[1
,3
]}

Sikora, Bozena ^{[1
,3
]}

Bowman, Elise D. ^{[2
]}

Harris, Curtis C. ^{[2
]}

Rusin, Marek ^{[1
,3
]}

机构：

[1] Maria Sklodowska Curie Mem Canc Ctr, Dept Tumor Biol, PL-44101 Gliwice, Poland

[2] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA

[3] Inst Oncol, Gliwice Branch, PL-44101 Gliwice, Poland

来源：

CELLULAR & MOLECULAR BIOLOGY LETTERS | 2010年 / 15卷 / 04期

关键词：

Single nucleotide polymorphism; XPA; Kozak sequence; Alternative splicing; Cancer risk; Reporter assay; NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-A; CELL LUNG-CANCER; XERODERMA-PIGMENTOSUM; DNA-REPAIR; HUMAN TISSUES; RISK; TRANSLATION; POPULATION; PROTEIN;

D O I：

10.2478/s11658-010-0032-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The XPA gene has a commonly occurring polymorphism (G23A) associated with cancer risk. This study assessed the functional significance of this polymorphism, which is localised near the translation start codon. Lymphoblastoid cell lines with alternative homozygous genotypes showed no significant differences in their XPA levels. The luciferase reporter assay detected no functional difference between the two sequences. Unexpectedly, we found that the alternatively spliced form of XPA mRNA lacked a part of exon 1. Only the reading frame downstream of codon Met59 was preserved. The alternative mRNA is expressed in various human tissues. The analysis of the 5'cDNA ends showed similar transcription start sites for the two forms. The in vitro expression of the alternative XPA labelled with the red fluorescent protein (mRFP) showed a lack of preferential nuclear accumulation of the XPA isoform. The biological role of the alternative XPA mRNA form remains to be elucidated.

引用

页码：611 / 629

页数：19

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