DRS1 (DROUGHT SENSITIVE 1, At1g80710) encodes a 516-residue WD40-repeat protein that is the Arabidopsis member of the WDR76/CMR1 subfamily (PANTHER PTHR14773:SF0), the same subfamily as human WDR76 and budding-yeast Cmr1. In those orthologs the protein is nuclear and chromatin-associated, binds DNA in vitro, relocalizes to nuclear foci under genotoxic stress and is linked to DNA-damage checkpoint adaptation; these properties are inherited by DRS1 phylogenetically but have not been tested in plants. DRS1 also carries a DWD (DDB1-binding WD40) motif, suggesting that it may act as a substrate receptor of CUL4-DDB1 ubiquitin ligases, although no DRS1 partner has been demonstrated. Genetically, two independent drs1 T-DNA alleles retain less water under drought and fail to reduce detached-leaf water loss in response to ABA, while ABA inhibition of germination is unaffected. The biochemical link between the conserved nuclear WD40 activity and this drought/ABA phenotype is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000792 heterochromatin | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The PAINT node PTN000381277 propagates heterochromatin from human WDR76 (Q9H967), which co-localizes with the heterochromatin proteins CBX1 and CBX5. DRS1, human WDR76 and yeast Cmr1 are all members of PANTHER subfamily PTHR14773:SF0, so DRS1 lies inside the inheriting clade. Reason: Challenging an IBA requires evidence that the target is outside the clade or has diverged. DRS1 is in the same SF0 subfamily as the human donor, and nothing in the Arabidopsis literature bears on its subnuclear localization in either direction, so the propagated localization is retained. It is non-core because the donor evidence is a co-localization with heterochromatin proteins in human cells, a sub-compartment that has not been examined for any plant member, and because the characterized DRS1 role is physiological. Supporting Evidence: PMID:27248496 WDR76 co-localizes to puncta with the heterochromatin proteins CBX1 and CBX5 PMID:25817432 WDR76 associated with chromatin in untreated cells and relocalized into nuclear foci under replication stress conditions |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: The IBA is seeded from yeast Cmr1 (SGD:S000002315), which binds DNA in vitro and accumulates on chromatin after UV irradiation. DRS1 sits in the same PTHR14773:SF0 ortholog subfamily, so the PAINT placement applies to it. Reason: DNA binding is the only molecular function the WDR76/CMR1 ancestral node carries, and it is consistent with the chromatin association of both yeast and human orthologs. There is no Arabidopsis evidence of loss or divergence. The term is kept at the broad level asserted by PAINT; it does not imply recognition of UV-damaged DNA or of a particular modified base (such as 5hmC), for which no plant evidence exists and genomic 5hmC is barely detectable in Arabidopsis. Accepted as the conserved core activity, recognising that it is phylogenetically inferred rather than measured for DRS1. Supporting Evidence: PMID:25817432 Cmr1 was described as a histone-related protein11, with DNA-binding capacity in vitro and with the ability to accumulate on chromatin in response to ultraviolet irradiation PMID:25817432 WDR76 is the closest orthologue of Cmr1 in higher eukaryotes |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is experimentally established for both seeding orthologs, yeast Cmr1 and human WDR76, and the PAINT node places it at the WDR76/CMR1 ancestor from which DRS1 descends. Reason: Two experimentally characterized orthologs from different eukaryotic supergroups (opisthokont fungi and animals) are nuclear, which supports placement of this localization at the ancestral node; DRS1 has no evidence of divergence. The deep-research report's statement that localization is unknown reflects the absence of a plant-specific experiment, not evidence against the inference. Supporting Evidence: PMID:25817432 Cmr1 (changed mutation rate 1) is a nuclear WD40 protein of unknown function PMID:25817432 WDR76 associated with chromatin in untreated cells and relocalized into nuclear foci under replication stress conditions |
| GO:0005634 nucleus | ISM GO_REF:0000122 | ACCEPT | Summary: AtSubP sequence-based prediction of nuclear localization; it agrees with the phylogenetically grounded IBA for the same term and with the nuclear localization of the yeast and human orthologs. Reason: Consistent with the IBA row for the same term. Retained without implying any Arabidopsis microscopy or fractionation result. Supporting Evidence: PMID:25817432 Cmr1 (changed mutation rate 1) is a nuclear WD40 protein of unknown function |
| GO:0009414 response to water deprivation | IMP PMID:20118918 Rational association of genes with traits using a genome-sca... | KEEP AS NON CORE | Summary: drs1-1 plants retained about 80% of wild-type water under drought, the defect co-segregated with the T-DNA as a single recessive locus, and an independent allele (drs1-2) reproduced it. The paper explicitly identifies At1g80710 as DRS1. Reason: Direct target-specific genetic evidence with two alleles. The gene was chosen from an AraNet network prediction, but the annotation rests on the mutant experiments, not the prediction. The molecular step DRS1 performs in the response is unknown, which the acts_upstream_of_or_within qualifier appropriately reflects. Kept as non-core. The term is as precise as the evidence allows, but it records a loss-of-function phenotype rather than an activity DRS1 performs, so it is not asserted as a core function; the conserved nuclear DNA-binding WD40 role is. Supporting Evidence: PMID:20118918 Under drought, mutant plants retained ~80% of the water of wild type PMID:20118918 An independent T-DNA allele (Salk_149366C) that we designate as drs1-2 exhibited the same phenotypes in relative water content following drought and ABA-insensitive water transpiration |
| GO:0009737 response to abscisic acid | IMP PMID:20118918 Rational association of genes with traits using a genome-sca... | KEEP AS NON CORE | Summary: Detached drs1 leaves were insensitive to the ABA-induced reduction in water loss, confirmed in a second allele, whereas ABA inhibition of germination was unaffected. Reason: Direct two-allele genetic evidence for a defect in one ABA response (leaf transpiration). The germination result shows that not all ABA responses depend on DRS1, so this annotation should not be expanded to ABA signaling generally or to an ABA receptor or signal-transduction activity. Kept as non-core for the same reason as GO:0009414. It is a loss-of-function phenotype with no known DRS1 step, not a participation claim. Supporting Evidence: PMID:20118918 The mutant was insensitive to ABA on water loss whereas the wild type lost significantly less water in the presence of 10 ΞΌM ABA PMID:20118918 ABA showed no effect on germination rate in the mutant (data not shown), indicating that not all ABA-mediated processes are affected in the mutant. |
| GO:0080008 Cul4-RING E3 ubiquitin ligase complex | ISS PMID:18223036 Characterization of Arabidopsis and rice DWD proteins and th... | KEEP AS NON CORE | Summary: This ISS rests on DRS1 carrying the DWD (DDB1-binding WD40) motif that Lee et al. (2008) used to define candidate CUL4-DDB1 substrate receptors, with PRL1 (AT4G15900), a DWD protein shown to bind DDB1, as the comparator. The human ortholog WDR76 (same PANTHER subfamily) has been reported to associate with Cul4-DDB1. Reason: Two consistent lines support the inference, the conserved DWD motif stated for DRS1 in its primary paper and the reported Cul4-DDB1 association of the orthologous human WDR76. PRL1 is not a DRS1 ortholog (it is in a different WD40 family), so the ISS transfers a motif-defined property, not a family function. Lee et al. confirmed DDB1 binding for only 11 Arabidopsis DWD proteins, and no DRS1-DDB1 or DRS1-CUL4 experiment exists. Nothing contradicts the inference, so it is retained as non-core; the substrate and any link to the drought phenotype are unknown. Supporting Evidence: PMID:20118918 Drs1 is a WD-40 repeat family protein containing a DWD (DDB1 binding WD40) motif PMID:18223036 We show by yeast two-hybrid and in vivo coimmunoprecipitation that 11 Arabidopsis DWD proteins directly interact with DDB1 and thus may serve as substrate receptors for the DDB1βCUL4 machinery. PMID:27248496 Intriguingly WDR76 was found to associate with the Cul4-DDB1 ubiquitin ligase complex |
| GO:2000001 regulation of DNA damage checkpoint | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Seeded from yeast Cmr1, whose deletion causes a defect in DNA-damage checkpoint adaptation. Human WDR76 is rapidly recruited to sites of laser-induced DNA damage. DRS1 inherits the process from the WDR76/CMR1 node (PTHR14773:SF0). Reason: The PAINT node is grounded in yeast experimental data, and a single seeding organism is not weak support for an IBA. DRS1 is in the same ortholog subfamily with no evidence of divergence; the drought/ABA phenotype neither supports nor contradicts a checkpoint role. Retained as non-core because no plant DNA-damage or checkpoint assay has been reported for DRS1 and its characterized role is physiological. Supporting Evidence: PMID:25817432 Deletion of CMR1 causes increased chromosome loss and mutation rates, a defect in DNA-damage checkpoint adaptation PMID:27248496 Here we report that WDR76 is rapidly and intensely recruited to regions of localized DNA damaged induced by UV-laser microirradiation. |
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Download this section (compressed HTML)Q: Which biochemical partners link DRS1 to ABA-dependent water retention, and is the DWD motif required for that function?
Q: Does DRS1, like yeast Cmr1 and human WDR76, bind DNA and relocalize to nuclear foci under genotoxic or proteotoxic stress, and is this conserved activity connected to the drought phenotype?
Experiment: Native-promoter DRS1-fluorescent protein fusion that complements drs1-1, imaged in roots and guard cells with and without genotoxic stress (MMS, UV) or proteasome inhibition, to test nuclear localization and stress-induced focus formation.
Experiment: Affinity purification-mass spectrometry or yeast two-hybrid of DRS1 with DDB1A/DDB1B, and complementation of drs1 with a DWD-motif mutant, to test whether DRS1 acts as a CUL4-DDB1 substrate receptor in drought responses.
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