Characterization of the human Rad51 genomic locus and examination of tumors with 15q14-15 loss of heterozygosity (LOH).
Human Rad51 (hRad51) has been found to be associated with BRCA1, BRCA2, and p53 either directly or indirectly and is one of at least eight human genes that are members of the Escherichia coli RecA/Saccharomyces cerevisiae Rad51 family thought to affect genomic stability through DNA recombination/repair processes. While inactivation of DNA mismatch repair clearly leads to instability of repeated sequences and to an increased risk for tumorigenesis, such a parallel for the RecA family members has not been reported. Recently, a high frequency of loss of heterozygosity at chromosome 15q14-15, near the genomic region containing hRad51, has been reported in human tumors (W. Wick et al., Oncogene, 12: 973-978, 1996). To determine whether hRad51 inactivation may be involved in the etiology of these tumors, we have characterized the hRad51 genetic locus and mapped it to chromosome 15q14-15 within the central region of loss of heterozygosity. However, single-strand conformational polymorphism analysis and direct sequencing of tumors did not reveal any mutations in the hRad51 coding sequence or intron/exon boundaries. We also examined the DNA methylation status of a CpG-rich region in the putative hRad51 promoter region. No indication of hypermethylation was found. These results suggest that hRad51 is not a tumor suppressor because it is either an essential gene, redundant gene and/or independent of the BRCA1/BRCA2 tumor suppressor pathway(s).
Schmutte
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Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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Rhiem
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Sadoff
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Schmutzler
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von Deimling
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Fishel
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D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015226:Dinucleoside Phosphates / Q000032:analysis; D005091:Exons; D006801:Humans; D007438:Introns; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D051135:Rad51 Recombinase; D011938:Rec A Recombinases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D051135:Rad51 Recombinase; D011938:Rec A Recombinases; D029701:Saccharomyces cerevisiae Proteins; C015772:CpG dinucleotide; C495151:RAD51 protein, S cerevisiae; C495153:RAD51 protein, human