Origin-Dependent Inverted-Repeat Amplification A Replication-Based Model for Generating Palindromic Amplicons 英文参考文献.docVIP

Origin-Dependent Inverted-Repeat Amplification A Replication-Based Model for Generating Palindromic Amplicons 英文参考文献.doc

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Origin-Dependent Inverted-Repeat Amplification A Replication-Based Model for Generating Palindromic Amplicons 英文参考文献

Viewpoints Origin-DependentInverted-RepeatAmplification:A Replication-BasedModelforGeneratingPalindromic Amplicons BonitaJ.Brewer*,CeliaPayen,M.K.Raghuraman,MaitreyaJ.Dunham DepartmentofGenomeSciences,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica Introduction (dsDNA)breakandimplicateDNAfusions (either homologous or non-homologous), Break-Induced Replication (BIR), Micro- composed of alleles from both homologs of one of the parents in a 2:1 ratio, consistent with the hypothesis that the event occurred in a meiotic or a pre- meiotic division [8,14,15]. In all cases of de novo triplications with an inverted central copy, the distal portion of the chromosome was retained. This finding appears to eliminate models such as the Breakage-Fusion-BridgemodelofMcClin- tock [17], at least in their simplest forms, as models that invoke a dsDNA break cannoteasilyexplaintheretentionofdistal sequences. Models proposed to explain the gener- ationofpalindromic(orquasipalindromic) structures during segmental amplification homology/Microsatellite-Induced Repli- cation(MMIR),and/orinvertedordirect- ly repeated sequences that adopt unusual secondary structures for their repair [4]. Fromthemolecularanalysis[7]ofayeast strainthatcontainsamplifiedcopiesofthe geneforthehighaffinitysulfurtransporter, SUL1[3],wederivedanewgeneralmodel that explains the generation of interstitial tandeminvertedrepeatarraysofchromo- some segments in yeast and in human cancers,andofdenovocongenitalinverted triplications and other chromosomal rear- rangements.Weproposethatcellscommit asingularerrorinreplication:theligation ofthenascentleadingstrandtothenascent laggingstrandatthereplicationfork.This modelcanpotentiallyexplaintheoriginof many palindromic rearrangements and their structural, enzymatic, and genetic requirements. almost invariably begin with double- stranded DNA breaks that are repaired indifferentways—forexample,byend-to- end fusion at short inverted repeats, by non-allelic homolo

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