ABSTRACT
The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility.
ABSTRACT
The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility.
ABSTRACT
The Ras superfamily of GTP binding proteins encompasses several gene families that regulate a plethora of events in the eukaryotic cell. Here we describe a novel branch of this superfamily which we have named RJLs. These are present in many unicellular organisms and also in deuterostomes but apparently missing in some intermediary phyla, suggesting an intriguing possibility of lateral gene transference between lower and higher eukaryotes. RJLs lack classical membrane targeting signals and the conserved glutamine residue that coordinates GTP hydrolysis in other proteins from the Ras superfamily. Interestingly, chordate orthologues are chimeras fused to "J" domains in their C-terminal, suggesting that these proteins recruit Hsc70 to specific sites in the cell. Expression analysis of RJLs from chordates suggests predominant expression in nervous tissues, possibly reflecting a role for RJLs in the development or maintenance of the sophisticated chordate nervous system.
