Microsoft Word - 02 11-155 王伟doc-鸡的端粒生物学研究

HEREDITAS(Beijing)20121,34(1):19―26ISSN0253-9772综述收稿日期:20110413;修回日期:20110628基金项目:(30972086)(973)(2009CB941604)作者简介:,,Tel:[phone];E-mail:[e-mail]通讯作者:,,,E-mail:[e-mail]网络出版时间:2011-10-1815:34:52URL::10.3724/SP.J.1005.2012.00019鸡的端粒生物学研究王伟,王珊珊,李辉,王宁,150030端粒是线性染色体末端的核蛋白“帽子”结构,其长度由端粒酶来维持。端粒对于维持基因组的稳定、防止细胞衰老和肿瘤发生具有重要的作用。鸡是遗传和发育研究的经典模式动物,随着鸡基因组学研究的不断深入,鸡的端粒和端粒酶研究取得了很大进展。文章综述了近年来鸡的端粒生物学研究进展,并提出了未来的研究方向。鸡;端粒;端粒酶;鸡端粒酶逆转录酶;鸡端粒酶RNATelomerebiologyofthechickenWANGWei,WANGShan-Shan,LIHui,WANGNingCollegeofAnimalScienceandTechnology,NortheastAgriculturalUniversity,Harbin150030,ChinaAbstract:Telomeres,thenucleoprotein“caps”protectingtheendsoflinearchromosomes,aremaintainedbytelomerase.Telomereshaveimportantrolesinmaintaininggenomicstabilityandpreventingsenescenceoroncogenesis.Chickenisaclassicalmodelanimalforgeneticanddevelopmentalstudies.Withfurtherdevelopmentofchickengenomics,greatpro-gresshasbeenmadeinresearchofchickentelomereandtelomerase.Thisreviewdescribesrecentadvancesandfuturere-searchdirectionsinchickentelomerebiology.Keywords:chicken;telomere;telomerase;chTERT;chTR,,90002004[1],10,1/3[2]381(ZW),(28,GGA11~38),[1],10[3],,;,20HEREDITAS(Beijing)201234,1,,,,,ATMATRDNA,[4]1.1DNA(TTAGGG)n,,T-loop[5~7],G3′,,,T-loop,D-loopT-loopDNA[5]1.22000,Delany[3]18(),(,4,100kb)(200kb)2002,Nanda[8](FISH)16(),(),(TTAGGG)n,,,Delany[3]3(1),,0.5~10kb,Bal31,,,[8];,10~40kb,Southernblotting,;,,200kb~4Mb,Bal31,Southernblotting()[3,9~11],10~15kb,30~200kb[12,13]SouthernblottingFISH[3,8~11]Delany[9]UCD001(,F0.9)UCD003(,F0.99)ADOLLine0(),(1),3,GGA1(p,q)GGA2(q)GGA3(q)GGAW(q)3图1鸡染色体的端粒序列图谱[14]3GGA1(3)GGA2GGA3GGAW,GGA9pGGAWq,GGA16pGGA28GGA1~4,GGA9,GGA1628,GGAZW;DNA;1:21GGA9(p)W(q),W(UCD0014Mb,UCD0032.8Mb),GGA16pGGA28(),,,,O'HareDelany[10](UCD001ADOLLine0)(DF-1)(DT40)4,,DF-1,17%,,UCD0015%,DT401.2%,0.3%,()[3,9~11]Rodrigue[11],,,,,,[9,11,15]1.3DNA-,DNA,Shelterin,TRF1TRF2POT1,DNATIN2TPP1RAP1[16]ShelterinDNA,DNA,DNA[16]4(TRF1TRF2POT1RAP1)[7,17~19],(TIN2TPP1)TRF146%,[17]TRF2(dimerisation)Myb-typeDNAORF,TRF2,TRF2[18]RAP136%,BRCA1MybRap,RAP1TRF2[19]POT1DNA,POT1T-loop,GT-loop[7]Tankyrase,Tankyrase1Tankyrase2,TRF1[17],,DNAA(RPA)Rad54Rad51BRCA1,,[20~23]SwanbergDelany[24]PCR(Chickenembryofibroblasts,CEFs)DT404(TRF1TRF2tankyrase1tankyrase2)c-mycchTERTchTR,7DT40()CEFs()CEFsTRF1TRF2,,TRF2:TRF1DT40tankyrase2(tankyrase2TRF1)CEFs,2RNADNA,(Telomerasereversetranscriptase,TERT)RNA(TelomeraseRNA,TR)TERT,TR,3′TTAGGG,,DNA22HEREDITAS(Beijing)2012342.1,,,,[25~30],[24,26,27,31],,[32],[29,33]()(),160bp[3],,[27,28,34][35](TR−/−)[32,36]12.22.2.1chTERT的结构特点(chTERT)mRNA4表1人、小鼠和鸡的端粒生物学的比较分析(TR/)10~15kb30~200kb8kb~4MbTERT—TR—497bp,2q21,1346TERT,v-Iv-IIv-IIIv-IV12AB′CDE,T[37,38](2)chTERT(humanTERT,hTERT)(mouseTERT,mTERT),45%41%,chTERT,v-I(1~196),v-II(495~531),v-III(554~588),v-IV(625~753),T(756~803),1(814~838),2(839~870),A(915~950),B′(1038~1072),C(1078~1094),D(1095~1120)E(1139~1149),chTERTv-I15,v-IV27,N(298,144)(2)C-(RT),chTERT5′-259bp+727bpCpG,-938bp5′+125bp80TERT5′,Sp1MAZ/Sp-1E-boxIk1NF-1AP-1,chTERT5′c-Ets2WT1,4c-Myb[39]2.2.2chTERT的剪接变体,TERT,TERT[40,41]Chang[40]7.52CEFsDT40chTERT,chTERT(T)(RT)19图2鸡、人和鼠TERT蛋白基序的相对位置和大小1:23,3,(2)hTERT,chTERT5(V4)A,α,8(V911121314)B',β[40]6(V235141518),V4,[40],chTERT[40]chTERTmRNA表2chTERT重要功能区域的剪接变体v-IVV1(),V3()TV2(,),V3(,)2V4(),V5()AV4()IFDV6–V14(,,)B′V9(),V11–V14(,,)CV15(,),V16(,)DV17–V19(,)IFDTERT[42]2.3RNARNA(chTR)465bpRNA,chTR,3763bp,5′604bpchTR465bp3′2694bp[43]chTR9q[43]TR,,TR,TR35()TR,TR8,5′3′CR1~CR8,90%,8TR3Pseudoknot/Template,CR4/CR5ScaRNA[44,45]Pseudoknot/TemplateCR1CR2CR3,Template(CR1)5′-CUAACCCU-3'[45],3′(CU),DNA[45,46]TR,[47]Pseudoknot(CR2/CR3)TR,PseudoknotTRTERT,Pseudoknot[47,48](Marek'sdiseasevirus,MDV)RNA(virusTR,vTR),vTRchTR88%,vTR8PseudoknotP2-helixP3-helix,vTRchTERT,vTRchTR6[44]CR4/CR5TRTERT2[47]ScaRNAH/ACABox(CR6-CR8)CR7,TRTR3′[49,50]MDVH-Box3′,vTR,[44]TR5′SP1GRc-mybERCCAAT,,Sp1ERCCAAT,Sp1,3[43]2.4chTERTchTRTR(humanTR,hTR)[38,51],hTERT,hTERT[52]mTERTmTR(mouseTR)O'HareDelany[53](E0~E19)24chTERTchTR,(E024HEREDITAS(Beijing)201234E1)chTERTchTR,,()chTERTchTR,,()chTRchTERT,chTERTchTR,chTR(chES)CEFsDT40chTERTchTR,chESchTERTchTR,CEFschTERTchTR,DT40chTERTchTR[28],chTERTchTR2.5(hTERT),,,,[54],hTERT[36,55],,,[55]2003,Fragnet[56],mTRhTRvTRchTRTR2005,Fragnet[44]chTERTchTR(vTR)hTERTCEFs,hTERT,[57],,chTR,chTR[53],RobbDelanychTR(,chTR),CEFs,,48chTR,chTERTCEFs(DT40HeLa),CEFs,,chTRchTERT,3,,,,,(1),;(2);(3);(4);(5),,,参考文献(References):[1]InternationalChickenGenomeSequencingConsortium(ICGSC).Sequenceandcomparativeanalysisofthechickengenomeprovideuniqueperspectivesonvertebrateevolution.Nature,2004,432(7018):695-716.[2]GregoryTR,NicolJA,TammH,KullmanB,KullmanK,LeitchIJ,MurrayBG,KapraunDF,GreilhuberJ,BennettMD.Eukaryoticgenomesizedatabases.NucleicAcidsRes,2007,35(S1):D332-338.[3]DelanyME,KrupkinAB,MillerMM.Organizationof1:25telomeresequencesinbirds:evidenceforarraysofextremelengthandforinvivoshortening.CytogenetCellGenet,2000,90(12):139-1