How Do Microbial Pathogens Make CENs 英文参考文献.docVIP

Pearls HowDoMicrobialPathogensMakeCENs? KaustuvSanyal* MolecularMycologyLaboratory,MolecularBiologyGeneticsUnit,JawaharlalNehruCentreforAdvancedScientificResearch,Jakkur,Bangalore,India WhatIstheLinkbetweenDrugResistanceand AneuploidyinMicrobialPathogens? point centromere but often lacks any protein binding sequence motifs or conserved pericentric repeats, and c) ‘‘large regional’’ CENsthatspanalongregion(.40kb–afewMbs)usuallyrichin repeats and often CENP-A-containing nucleosomes are inter- In a variety of pathogens, drug resistance and aneuploidy are intimatelyassociated.Anueploidyisbelievedtoalterthedosageof certaingenesthatcanimpartdrugresistance.Generationofanew chromosomebyduplicationofchromosomesegmentsfollowedby telomere addition in a pathogenic yeast Candida glabrata [1] and isochromosome formation by breakage of chromosome 5 at the centromerefollowedbyjoiningtwoidenticalarmsofchromosome 5inanopportunisticyeastCandidaalbicans[2]havebeenshownto occur frequently in drug-resistant isolates. Fluconazole-resistant strains of another pathogenic fungus, Cryptococcus neoformans , have been shown to be disomic for certain chromosomes [3]. Experimental evidence suggests that acquisition of chromosomes by the plant pathogenic fungus Fusarium can convert a non- pathogenic strain to a pathogenic one [4]. Anueploidy has been showntobethecauseofdrugresistanceintheprotozoanparasite Leishmaniaaswell[5]. spersed with H3-containing nucleosomes. Formation of a kinetochoreonmostpointCENsinitiateswithbindingofaDNA sequence-specifickinetochoreprotein[8].Incontrast,severallines ofevidencesuggestthatepigeneticfactors,nottheDNAsequence alone,alsocontributetocentromereidentityinorganismscarrying smallorlargeregionalcentromeres[8–10]. HowAreCentromeresOrganizedinFungal Pathogens? The pathogenic fungi show wide diversity in CEN structure (Figure 1; reviewed in [11]). C. glabrata, a human pathogenic ascomycetousyeast,hasshortpointCENs.CENsinC.glabrata ,like thewell-studiedCENsofb