Drosophila SPF45 A Bifunctional Protein with Roles in Both Splicing and DNA Repair 英文参考文献.docVIP

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Drosophila SPF45 A Bifunctional Protein with Roles in Both Splicing and DNA Repair 英文参考文献.doc

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Drosophila SPF45 A Bifunctional Protein with Roles in Both Splicing and DNA Repair 英文参考文献

DrosophilaSPF45:ABifunctionalProtein withRolesinBothSplicingandDNARepair Ahmad Sami Chaouki, Helen K.Salz* DepartmentofGenetics,SchoolofMedicine,CaseWesternReserveUniversity,Cleveland,Ohio,UnitedStatesofAmerica The sequence of the SPF45 protein is significantly conserved, yet functional studies have identified it as a splicing factorinanimalcellsandasaDNA-repairproteininplants.Usingacombinedgeneticandbiochemicalapproachto investigatethisapparentfunctionaldiscrepancy,weunifyandvalidatebothofthesestudiesbydemonstratingthat theDrosophilamelanogasterproteinisbifunctional,withindependentfunctionsinDNArepairandsplicing.Wefind thatSPF45associateswiththeU2snRNPandthatmutationsthatremovetheC-terminalendoftheproteindisruptthis interaction.Althoughanimalscarryingthismutationareviable,theyareneverthelesscompromisedintheirabilityto regulateSex-lethalsplicing,demonstratingthatSex-lethalisanimportantphysiologicaltargetofSPF45.Furthermore, these mutant animals exhibit phenotypes diagnostic of difficulties in recovering from exogenously induced DNA damage.TheconclusionthatSPF45functionsintheDNA-repairpathwayisstrengthenedbyfindingbothgeneticand physical interactions between SPF45 and RAD201, a previously uncharacterized member of the RecA/Rad51 protein family.TogetherwithourfindingthattheflySPF45proteinincreasesthesurvivalrateofmutagen-treatedbacteria lacking the RecG helicase, these studies provide the tantalizing suggestion that SPF45 has an ancient and evolutionarilyconservedroleinDNArepair. Citation:ChaoukiAS,SalzHK(2006)DrosophilaSPF45:AbifunctionalproteinwithrolesinbothsplicingandDNArepair.PLoSGenet2(12):e178.doi:10.1371/journal.pgen. 0020178 the nonhomologous SPF45 gene can functionally comple- ment recG is not known, this ill-de?ned function is likely to Introduction Assigning function to a newly discovered protein relies heavily on our understanding of similar proteins in other species. While for the most part the convergence of information from multiple systems poi