Human Molecular Genetics, Vol 6, 1057-1062, Copyright © 1997 by Oxford University Press
CF Xu, MA Brown, H Nicolai, JA Chambers, BL Griffiths and E Solomon
To study the regulation of BRCA1 gene expression and the potential
importance of dysregulation of this gene in breast and ovarian cancer, we
have examined the 5' region of the human BRCA1 gene in detail. We have
identified a new gene, NBR2, which is partially related to the NBR1 gene
(formerly known as 1A1-3B and mapping directly adjacent to the pseudo-BRCA1
gene) and which lies head to head with the BRCA1 gene. The physical
distance between the transcription start sites of the NBR2 and BRCA1 genes
is 218 bp, suggesting that regulation of the expression of both genes may
be co-ordinated through a bi-directional promoter. The NBR2 gene contains
five exons spanning a genomic region of approximately 30 kb between the
BRCA1 and pseudo-BRCA1 genes. Northern analysis showed that the NBR2 gene
is expressed in all the tissues examined. The NBR2 cDNA contains an open
reading frame of 112 amino acids and is predicted to encode a protein of
approximately 12 kDa. Single-strand conformation polymorphism (SSCP)
analysis of the NBR2 gene failed to identify any mutations in either breast
or ovarian cancer, suggesting that if the NBR2 gene is involved in the
development of these cancers, other mechanisms for tumorigenesis may exist.
Hybridisation of NBR2 probes to zoo blots showed that the NBR2 gene is
present in human and other primates. No hybridisation to DNA from other
species was observed, suggesting that genomic elements controlling BRCA1
expression may differ between species.
ARTICLES
Isolation and characterisation of the NBR2 gene which lies head to head with the human BRCA1 gene
Somatic Cell Genetics Laboratory, Imperial Cancer Research Fund, London, UK. xu@icrf.icnet.uk
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