Although DT40 cells deleted for both and did not show a higher SCE level compared to the cells displayed a hyper-SCE phenotype when cells were treated with the ICL agent mitomycin C (Wang et al
Although DT40 cells deleted for both and did not show a higher SCE level compared to the cells displayed a hyper-SCE phenotype when cells were treated with the ICL agent mitomycin C (Wang et al., 2003). genome-wide interactions with the helicase (or any other gene) in question using a facile methodology, and also ranked candidate genetic interactions. The results from the study by the Boeke lab suggested different roles for Srs2 and Sgs1 in the response to replicational stress. Srs2 was predicted to operate in a damaged DNA replication fork processing role, whereas Sgs1 was more specifically tailored to have roles in rDNA replication, DNA topology, or lagging strand synthesis. Moreover, Sgs1 cIAP1 Ligand-Linker Conjugates 15 hydrochloride and Srs2 were predicted to operate in parallel pathways cIAP1 Ligand-Linker Conjugates 15 hydrochloride in a DNA damage checkpoint pathway by separately transducing the replicational stress signal. Overall, this study provided a first proof of principle that helicase genetic interaction networks exist and can be dissected. Moreover, the results were consistent with earlier evidence that the synthetic lethal interaction of and (Lee et al., 1999) can be attributed to accumulation of toxic recombination intermediates that can be suppressed by the additional loss of HR genes or (Gangloff et al., 2000). In 2005, the Campbell lab employed a synthetic genetic array analysis (SGA) using as the query yeast cIAP1 Ligand-Linker Conjugates 15 hydrochloride helicase gene (Budd et al., 2005). Dna2 is best known for its role during Okazaki fragment processing, a key aspect of cellular lagging strand DNA replication. Using two well know conditional alleles of gene-interacting pathways defined a network of proteins previously implicated to operate at the replication fork and important for genomic stability. These included proteins involved in the processes of Okazaki fragment processing, DNA repair, and chromatin remodeling. genetically interacted with polymerase delta, other DNA helicases, and genes that are synthetic lethal with and double mutant showed a severe growth defect and increased sensitivity to a variety of DNA damaging agents compared to the single mutants ITM2A (Kato and Inoue, 2006), suggesting the two RecQ helicases operate in parallel pathways of the DNA damage response. Importantly, the growth defect of the double mutant was suppressed by a third mutation in the homolog double mutant was suppressed by mutation in the mammalian Ku80 homolog double mutant. However, the growth defect of the double mutant was not suppressed by the mutation, consistent with the idea that HR is responsible. Based on their genetic results, the authors proposed that the two RecQ homologs in play a role in the suppression of spontaneous DSBs. Given the strong interest in DNA strand break repair as a target for inhibition in anti-cancer strategies, the genetic interactions between RecQ genes demonstrated in and other model systems are likely to be relevant. Drosophila BLM A common theme cIAP1 Ligand-Linker Conjugates 15 hydrochloride in helicase functions during cellular replication or repair is the interaction of these proteins with structure-specific nucleases. A good example of the myriad of physical and functional interactions between helicases and nucleases is that of the RecQ helicases and Rad2 nucleases (Sharma et al., 2008). WRN helicase, defective in Werner syndrome, stimulates the DNA cleavage activity catalyzed by Flap Endonuclease 1 (FEN1), a nuclease that is implicated in Okazaki fragment processing and base excision repair, through a physical protein interaction (Brosh et al., 2001; Brosh et al., 2002). The WRN: FEN1 interaction was shown to be important in cellular DNA replication (Sharma et al., 2004b), and the two proteins are closely associated with each other in human cells at arrested replication forks (Sharma et al., 2004a). BLM was also show to interact with FEN1 (Sharma et al., 2003b). Protein interactions of.