Disease relevance of RAD54L

• Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker [1].
• BACKGROUND: RAD54L (OMIM 603615, Locus Link 8438) has been proposed as a candidate oncosupressor in tumours bearing a non-random deletion of 1p32, such as breast or colon carcinomas, lymphomas and meningiomas [1].
• Single nucleotide polymorphisms of RecQ1, RAD54L, and ATM genes are associated with reduced survival of pancreatic cancer [2].
• Using a panel of 38 1p and five 1q markers, we therefore performed deletion-mapping analysis on a series of 35 oligodendrogliomas, which were also studied for mutations in the hRAD54 gene [3].

High impact information on RAD54L

• The median survival time was 19.2, 14.7, and 13.2 months for the RecQ1 159 AA, AC, and CC genotypes, and 16.4, 13.3, and 10.3 months for RAD54L 157 CC, CT, and TT genotypes, respectively [4].
• Severe combined immunodeficient cells expressing mutant hRAD54 exhibit a marked DNA double-strand break repair and error-prone chromosome repair defect [5].
• Double-mutant cells demonstrate an increase in ionizing radiation sensitivity and a decrease in DNA DSB repair as compared with either single mutant, whereas single-mutant hRAD54 cells exhibit a wild-type phenotype [5].
• Double-mutant cells were created by expressing a dominant mutant hRAD54 protein in a DNA-dependent protein kinase (DNA-PK)-deficient severe combined immunodeficient cell line [5].
• We found that the levels of hHR54 mRNA increased in late G1 phase, as has been found for RAD54 mRNA [6].

Biological context of RAD54L

• Frequent loss of heterozygosity for the 2290C/T SNP in meningiomas allowed to further narrow the 1p32 consensus region of deletion in meningiomas to either 2.08 Mbp - within D1S2713 (44.35 Mbp) and RAD54L (46.43 Mbp) - or to 1.47 Mbp - within RAD54L and D1S2134 (47.90 Mbp) - according to recent gene mapping results [1].
• The hHR54 gene was mapped to chromosome 1p32, and the hHR54 protein was located in the nucleus [6].
• Here we demonstrate that telomere elongation observed in murine scid cells can be reversed by expressing mutant hRAD54, a protein involved in homologous recombination [7].
• We used PCR/SSCP to examine all 18 exons of the hRAD54 gene for mutations in 25 tumors, but the mobility shifts detected corresponded to previously identified polymorphic changes: T-to-C transition at nucleotide 2865 (with no amino acid change) and at nucleotide 3008, at the 3' untranslated region [3].

Analytical, diagnostic and therapeutic context of RAD54L

• Silencing of the SNF2/SWI2 family members RAD54L or RAD54B, which are important for HR, reduced the rate of stable rAAV gene targeting approximately 5-fold [8].
• In addition, we measured recombination rates at telomeres using chromosome orientation fluorescence in situ hybridization (CO-FISH) and found that these are elevated in scid cells in comparison with control cells, or significantly reduced in scid cells expressing mutant hRAD54 [7].

References