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

Cellular & Molecular Biology Letters

Małgorzata Krześniak¹  Rasa Vaitiekunaite¹  Dorota Butkiewicz¹  Bożena Sikora¹  Marek Rusin¹  Curtis C. Harris²  Elise D. Bowman² 

[1] Department of Tumour Biology, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland$$;Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, USA$$

关键词: Single nucleotide polymorphism;    XPA;    Kozak sequence;    Alternative splicing;    Cancer risk;    Reporter assay;   

DOI  :  10.2478/s11658-010-0032-2

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 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.

【 授权许可】

Unknown