Disease relevance of RAD1

• The human RAD1 locus was mapped to human chromosome 5p13.2, a locus frequently altered in non-small-cell lung cancer and bladder cancer [1].
• The human RAD1 gene could be localized on human chromosome 5p13, a region that has been implicated in the etiology of small cell lung carcinomas, squamous cell carcinomas, adenocarcinomas, and bladder cancer [2].
• We show that human RAD1 partially complements the hydroxyurea and ionizing radiation hypersensitivities of a S. pombe rad1 mutant, suggesting phylogenetic conservation of the DNA damage and replication checkpoints [1].
• These deficiencies may perpetually generate DNA strand breakage as we have found chromosomal abnormalities in Rad1-depleted cells [3].
• Like As2O3, PAT was found to inhibit cell growth of various lymphoid cell lines, deriving from either acute lymphoid leukaemias (Jurkat, Molt-4 and Nalm-6) or lymphomas (Daudi, Raji and Rec1) [4].

High impact information on RAD1

• Plasmids containing Z-DNA stretches can be paired and linked by combined action of Ustilago rec1 protein and topoisomerase [5].
• Equilibrium and kinetic studies show that rec1 protein appears to have a strong Z-DNA binding site that binds Z-DNA 75 times tighter than the B form of the DNA [6].
• Synapsis promoted by Ustilago rec1 protein [7].
• ATP-dependent reannealing of complementary single strands was not detectable in the rec1 mutant of Ustilago, which is deranged in meiotic recombination, as complete tetrads are rare, and is defective in radiation-induced mitotic gene conversion [8].
• The human gene HRAD1 is located on chromosome 5p13 and is most homologous to S. pombe rad1(+) [9].

Biological context of RAD1

• On the basis of sequence homology, yeast and human Rad1, Rad9, and Hus1 protein homologs are predicted to structurally resemble the sliding clamp PCNA [10].
• The Schizosaccharomyces pombe Rad1 protein is an essential component of cell cycle checkpoints activated by both types of genomic stress [1].
• We show that RAD1 is an essential gene for sustained cell proliferation and that loss of Rad1 causes destabilization of Rad9 and Hus1 and consequently disintegration of the sliding-clamp complex [3].
• Growing evidence suggests that the Rad9/Rad1/Hus1 cell-cycle checkpoint complex (9-1-1 complex), which is recruited to DNA lesion upon DNA damage, plays a major role in DNA repair [11].
• A combined (GTT)n (ATT)n trinucleotide-repeat polymorphism designated as RAD1 has been identified at intron 2 of the rad gene on chromosome 16q [12].

Anatomical context of RAD1

• Northern blot analysis indicates that HUS1 is expressed in different tissues, but the mRNA is most predominant in testis where high levels of RAD1 and RAD9 message have been detected [13].
• Mitoxantrone, a topoisomerase II inhibitor, induced a strong cytotoxic effect in three cell lines (JVM-2, REC-1, and Granta 519), and in primary MCL cells [14].
• We sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes [15].
• Our results suggest that culture-expanded hREC have the potential to colonize collagen-coated biomaterials and to regenerate epithelial cell types for tracheal tissue engineering [16].

Physical interactions of RAD1

• The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1 [17].
• Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells [18].

Regulatory relationships of RAD1

• The Schizosaccharomyces pombe rad1+ cell cycle checkpoint control gene is required for S-phase and G2/M arrest in response to both DNA damage and incomplete DNA replication [2].

Other interactions of RAD1

• The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1 [19].
• Rad17, Rad1, Hus1, and Rad9 are key participants in checkpoint signaling pathways that block cell cycle progression in response to genotoxins [20].
• A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes an exonuclease [21].

Analytical, diagnostic and therapeutic context of RAD1

• Chromosomal localization by fluorescence in situ hybridization indicates that Hrad1 is located on chromosome 5p13 [21].
• High-purity (greater than 95%) hREC preparations were selected for experiments, based on immunofluorescence with acetylated low density lipoprotein (LDL) and anti-factor VIII-related antigen [15].

References