Studies are underway evaluating patients with other HR defects like PTEN and FA pathway defects.
Synthetic lethality might be compromised because cancers may employ multiple pathways to overcome a defect in one DNA repair pathway [31].
On the other hand, when a disease has defects in multiple pathways representing distinct biology, a pathway-guided combination therapy may be employed in the clinic.
Overall, these studies suggest that, like many cancer predisposition syndromes such as HNPCC, IgAD and CVID may be a heterogeneous class of diseases due to defects in multiple pathways.
Loss of Fig4/FIG4 causes a decrease of PtdIns 3,5) P2 levels and defects in multiple pathways in the endomembrane system.
The involvement of ERCC1/XPF as a nuclease in multiple repair pathways in addition to NER (interstrand crosslink repair and DSB repair) raises the question whether the neurodegenerative changes observed were caused by deficiency in one of these pathways, or by synergistic deleterious actions resulting from defects in multiple pathways [ 26, 65].
How mutant Htt leads to neurodegeneration is still under investigation, but may involve defects associated with multiple pathways [ 2].
Motor neuron death in ALS is a complex process, and may involve multiple pathways including formation of protein aggregates, axonal transport defects, oxidative damage, mitochondrial defects, and alterations in calcium homeostasis [6].
As a consequence of the multiple pathways acting in concert, the cell-cycle defects increase in severity upon disruption of two or more parallel pathways.
We did find Dfs spanning one known gene, sidestep (side), but had classified these as affecting multiple pathways, since side mutants also have SNa and ISN defects [17].
