High impact information on Rad54l

• We have analyzed the phenotype of mouse RAD54-/- (mRAD54-/-) cells [1].
• Thus, mRAD54 is not required for the recombination processes that generate functional immunoglobulin and T cell receptor genes [1].
• We show that Lig4 and Rad54 cooperate to support cellular proliferation, repair spontaneous DSBs, and prevent chromosome and single chromatid aberrations [2].
• These findings demonstrate a role for NHEJ in the repair of DSBs that occur spontaneously during or after DNA replication, and reveal overlapping functions for NHEJ and Rad54-dependent HR in the repair of such DSBs [2].
• We have combined mutations in factors from both repair pathways, the HR protein Rad54 and the DNA-end-binding factor Ku80, which has a role in NHEJ [3].

Biological context of Rad54l

• Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability [2].
• Role of mammalian Rad54 in telomere length maintenance [4].
• Consistent with this observation, DNA damage-induced sister chromatid exchange was reduced in mRAD54-deficient cells [5].
• Our results suggest that mRAD54 promotes gene conversion with predominant use of the sister chromatid as the repair template at the expense of error-prone SSA [5].
• In this study, we analyzed the effect of mRAD54, a gene involved in homologous recombination, on the repair of a site-specific I-SceI-induced DSB located in a repeated DNA sequence in the genome of mouse embryonic stem cells [5].

Anatomical context of Rad54l

• These results indicate that mouse B cells must use factors for promoting homologous recombination that are distinct from the Rad54 proteins important in homology-based chicken Ab gene recombinations [6].
• The level of mHR54 mRNA was elevated in organs of germ cell and lymphoid development and increased mHR54 expression correlated with the meiotic phase of spermatogenesis [7].
• Wortmannin radiosensitization was observed in Chinese hamster cells (V79-B310H , CHO-K1), mouse mammary carcinoma cells (SR-1), transformed human fibroblast (N2KYSV), chicken B lymphocyte wild-type cells (DT40), and chicken Rad54 knockout cells (Rad54-/-) [8].
• Cells deleted for Brca2 exon 27 are hypersensitive to gamma-radiation, streptonigrin, mitomycin C and camptothecin and mildly resistant to ICRF-193 which is similar to HR defective cells null for Rad54 [9].

Regulatory relationships of Rad54l

• We discuss our results with respect to two models that describe how Rad54 stimulates Rad51-mediated DNA strand invasion [10].

Other interactions of Rad54l

• Two major complementary double-strand break (DSB) repair pathways exist in vertebrates, homologous recombination (HR), which involves Rad54, and non-homologous end-joining, which requires the DNA-dependent protein kinase (DNA-PK) [11].
• Rad51 forms a nucleoprotein filament on single-stranded DNA (ssDNA) that mediates pairing with and strand invasion of homologous duplex DNA with the assist of Rad54 [10].

Analytical, diagnostic and therapeutic context of Rad54l

• Gene targeting experiments demonstrate that homologous recombination in mRAD54-/- cells is reduced compared to wild-type cells [1].

References