Captulo 3 NUCLEO Noes gerais

o maior organelo da clula Contem a quase totalidade do DNA e tem os mecanismos para a sntese do RNA Em geral esfrico mas pode ter outras formas como alongada ou bilobar A maior parte das clulas tem apenas um ncleo mas algumas como os osteoclastos tm vrios Os eritrocitos no tm ncleo Na fig. 3.1 est esquematizada a estrutura do ncleo

http://cellbio.utmb.edu/cellbio/nucleus.htm Cortesia de Gwen V.Childs Univ. of Arkansas for Medical Sciences

http://universe-review.ca/R10-01-cellnucleus.htm

http://en.wikipedia.org/wiki/Cell_nucleus Fig. 3.1 Estrutura do nucleo

Membrana nuclear Esta tem dois folhetos constituindo as membranas internas e externa

Membrana interna Tem cerca de 6 nm de espessura Est em contacto com um denso reticulado de filamentos intermdios, a lmina nuclear Membrana externa Tambm tem cerca de 6 nm de espessura Continua-se com o RER A sua superficie citoplasmica est rodeada por uma malha laxa e delgada de vimentina Tem ribosomas que sintetizam as protenas transmembranarias Cisterna perinuclear o espao entre as duas membranas Tem l0 a 30 nm

Poros nucleares Em certos pontos as membranas interna e externa fundem-se criando aberturas, os poros nucleares que permitem a comunicao do ncleo com o citoplasma

cross section of a nuclear pore on the surface of the nuclear envelope (1). Other diagram labels show (2) the outer ring, (3) spokes, (4) basket, and (5) filaments.
http://en.wikipedia.org/wiki/Cell_nucleus fig. 3.2- poro nuclear

Dispe de vrios canais de 9 a 11 nm de dimetro que permitem a difuso de ies e molculas pequenas

As molculas de dimetro superior a 11nm so transportadas por receptores, processo necessitando de energia Para este transporte so necessrias protenas especificas, as exportinas que transportam macromoleculas como o RNA do musculo para o citoplasma e as importinas do citoplasma para o ncleo A aco destas protenas regulada pelas protenas Ran que se unem ao GTP As protenas que entram no ncleo tm uma sequencia peptidica definida, a NLS ( Nuclear Localisation Sequence) que reconhecida por transportadores citoplasmicos que a transportam para o poro

Complexo do poro nuclear 80 a 100 nm de dimetro Abarca as duas membranas nucleares Tem cerca de 50 proteinas, as nucleoporinas Est composto por trs estruturas proteicas sobrepostas parecidas a anis que se ligam mediante uma srie de raios dispostos de forma vertical Anel citoplasmico 8 subunidades Situado no bordo da superficie citoplasmica do poro Cada subunidade possui uma protena Ram Anel mdio Tem 8 proteinas transmembranarias que se projectam para o lume do poro e da cisterna Estas protenas semelhantes a raios fixam as glicoproteinas deste complexo dentro do bordo do poro No centro do anel mdio encontra-se um transportador que restringe a difuso passiva e se vincula a complexos proteicos adicionais que facilitam o transporte

Anel nucleoplasmico Encontra-se no bordo da superficie membranaria anlogo ao anel citoplasmico Facilita a sada de RNA

http://www.scripps.edu/~stoffler/proj/NPC/npc.html

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.2157 fig. 3.3 Estrutura do poro nuclear

Cromatina

Definio A cromatina uma estrutura que permite que mais de um metro de DNA se condense no pequeno volume do nucleo composta por DNA e protenas A maior parte das protenas so histonas

http://sgi.bls.umkc.edu/waterborg/chromat/chroma01.html Fig. 3.4 - Cromatina

Nucleosomas As unidades fundamentais da cromatina so os nucleossomas So constitudos por DNA e histonas A sua estrutura fornece o primeiro nvel de compactao do DNA no ncleo Esto espaados regularmente ao longo do genoma para formar um nucleofilamento com altos nveis de compactao

http://sgi.bls.umkc.edu/waterborg/chromat/chroma04.html Fig. 3.5 Histonas

Estrutura Os nucleossomas so constituidos por dimeros de quatro espcies de histonas H2A, H2B, H3 e H4 Formam a partcula central do nucleossoma volta do qual esto enrolados 147 pares de bases do DNA Cada nucleossoma est ligado a outro por um DNA ligador, ocupado por uma nica molcula de H O nucleossoma constitudo por uma particula central e uma regio de ligao que liga as partculas centrais adjacentes A particula central um octamero resultante da reunio de dois tetrameros H2B-H2AS,H4-H3)

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.html Cortesia de John W.Kimbal Fig. 3.6 - Nucleosoma e DNA ligador

Cada uma destas histonas contem dois domnios diferentes um pregueado que medeia as reaces histona-histona e histona-DNA e uma cauda NH2 terminal que sofre modificaes pstraducionais

Modificaes ps-traducionais Os aminocidos da cauda podem sofrer modificaes ps-traducionais, como sejam a acetilao da lisina, a metilao da lisina e arginina e a fosfatao da serina e treonina Estas modificaes fazem-se quase sempre nas caudas das H3 e H4

http://sgi.bls.umkc.edu/waterborg/chromat/chroma14.html Fig. 3.7 Modificaes das histonas

Muitas destas transformaes so reversveis No caso das acetilaes h um equilbrio entre as histona aciltransferases (HAT) e as histona desacetilases (HDAC) Estas modificaes tm geralmente a ver coma activao e a inibio de genes Na H3 a metilao da lisina4 est associada com genes activos e a da lisina com genes inactivos A fosfatao torna os cromosomas mais compactos, preparados para a mitose BIBLIOGRAFIA SOBRE CROMATINA

http://sgi.bls.umkc.edu/waterborg/chromat/chromatn.html http://www.chromatin.us/chrom.html http://cellbio.utmb.edu/Cellbio/nucleus2.htm http://en.wikipedia.org/wiki/Chromatin http://www.portfolio.mvm.ed.ac.uk/studentwebs/session4/3/chromatin.htm

http://www.chromatin.net/ http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.section.618
Eucromatina

http://www.euchromatin.net/

BIBLIOGRAFIA SOBRE O NUCLEO

http://cellbio.utmb.edu/cellbio/nucleus.htm http://www.cytochemistry.net/Cell-biology/nucleus.htm http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.html http://en.wikipedia.org/wiki/Cell_nucleus Membrana nuclear http://en.wikipedia.org/wiki/Nuclear_envelope Metabolismo das histonas no ncleo http://sgi.bls.umkc.edu/waterborg/chromat/chroma14.html http://www.web-books.com/MoBio/Free/Ch4G3.htm Nucleolo http://en.wikipedia.org/wiki/Nucleolus https://npd.hgu.mrc.ac.uk/compartments/nucleolus.html Ilustraes- nucleolo http://www.uni-mainz.de/FB/Medizin/Anatomie/workshop/EM/EMNucleolus.html Poros nucleares http://virologie.free.fr/documents/virologie/04-transport_nucleaire/transport_nucleaire.htm http://en.wikipedia.org/wiki/Nuclear_pores Transporte nuclear http://virologie.free.fr/documents/virologie/04-transport_nucleaire/transport_nucleaire.htm http://en.wikipedia.org/wiki/Nuclear_transport Animaes- transporte nuclear http://sspatel.googlepages.com/nuclearporecomplex

Nucleosomas http://www.accessexcellence.org/RC/VL/GG/nucleosome.html http://en.wikipedia.org/wiki/Nucleosome http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.html http://www.mol.biol.ethz.ch/groups/richmond/projects/nucleosome http://www.callutheran.edu/Academic_Programs/Departments/BioDev/omm/nucleosome/nucleosom e.htm Animaes- nucleosoma http://www.sumanasinc.com/webcontent/animations/content/organelles.html Ilustraes nucleosoma http://cmgm.stanford.edu/biochem201/Slides/Chromatin%20Structure/04%20Nucleosome%20Mode l.JPG http://sgi.bls.umkc.edu/waterborg/chromat/chroma09.html

Estrutura dos cromosomas Durante a maior parte da vida da clula, os cromosomas no so visveis ao microscpio Antes da clula dividir, o cromosoma duplica -se na fase S do ciclo celular Os cromosomas duplicados ou diades so mantidos juntos no centro pelo centromero

http://ghr.nlm.nih.gov/handbook/basics/chromosome Fig. 3.8 - Cromossomas

Enquanto ligados os cromosomas duplicados chamam-se cromatides irms O cinetocoro um complexo de protenas situado no centro do centromero sendo o ponto de insero que separaro as cromatides irms na anafase

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Chromosomes.html Cortesia de John W.Kimbal

http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/cell.f04/cellf04.html

http://www.web-books.com/MoBio/Free/Ch1C3.htm fig.3.9- cromatides

Cada cromossoma tem dois braos separados pelo centrmero, o brao longo ou q e o brao curto ou p Nmero de cromosomas O nmero de cromosomas especfico para cada espcie e constitui o genoma

http://www.web-books.com/MoBio/Free/Ch1C2.htm

Os seres humanos tm 46 cromosomas agrupados em 23 pares Em cada par cada cromosoma provm de cada um dos pais

cleo os

22 pares so iguais no homem e na mulher designando-se como autosomas O outro par determina o gnero, masculino ou feminino so os cromosomas sexuais A mulher tem dois cromosomas X (XX) e o homem um X e um Y B(XY) As clulas que contm pares de cromosomas (2n) chamam-se diploides As clulas germinais so aploides pois nelas s se encontra um membro de cada par (1n) Cariotipo O cariotipo o conjunto de rodos os cromossomas, ordenados pelo tamanho

http://www.web-books.com/MoBio/Free/Ch1C3.htm Fig. 3.10 cariotipo

Cromosomas sexuais Os cromossomas sexuais definem o sexo. O homem tem um cromossoma X e um Y e a mulher dois X.Na fecundao ligam-se um cromossoma do pai e um da me, resultando desta combinao a definio do sexo.

http://www.web-books.com/MoBio/Free/Ch1C4.htm Fig. 3.11 Cromossomas sexuais

BIBLIOGRAFIA SOBRE CROMOSSOMAS

http://en.wikipedia.org/wiki/Chromosome http://biology.unm.edu/ccouncil/Biology_112/Summaries/Sex.html http://ghr.nlm.nih.gov/chromosomes http://www.usd.edu/med/som/genetics/curriculum/1CHROM1.htm http://www.bioscience.org/urllists/chromos.htm http://www.nlm.nih.gov/medlineplus/ency/article/002327.htm http://www.ornl.gov/sci/techresources/Human_Genome/launchpad/ http://learn.genetics.utah.edu/content/begin/traits/

Cromatides http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Chromosomes.html http://en.wikipedia.org/wiki/Chromatid http://www.bio-medicine.org/biology-dictionary/Chromatid/ Cromossomas sexuais http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/SexChromosomes.html Estrutura dos cromossomas http://www.slic2.wsu.edu:82/hurlbert/micro101/pages/Chap8.html http://employees.csbsju.edu/hjakubowski/classes/ch331/DNA/oldnastructure.html http://cellbio.utmb.edu/Cellbio/nucleus2.htm

Aneuploidia Na aneuplodia existe um nmero anormal de cromosomas No sindroma de Down h trs cromosomas 21 (trisomia 21)

BIBLIOGRAFIA SOBRE DOENAS CROMOSSOMICAS

Aberraes cromossmicas http://atlasgeneticsoncology.org/Educ/PolyMecaEng.html http://www.chromodisorder.org/CDO/General/IntroToChromosomes.aspx http://www.med.univ-rennes1.fr/etud/pediatrie/aberrations_chromosomiques.htm http://www.web-books.com/MoBio/Free/Ch8E.htm Aneuploidia variegata em mosaico http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=257300

Cromosoma 4 Acondroplasia Coreia de Huntington Wolf Hirschorn http://rarediseases.about.com/cs/chromosome345/a/042404.htm http://en.wikipedia.org/wiki/Wolf-Hirschhorn_syndrome http://www.orpha.net/data/patho/GB/uk-WHS.pdf http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=whs http://emedicine.medscape.com/article/950480-overview http://www.ibis-birthdefects.org/start/wolfhirs.htm http://www.wrongdiagnosis.com/news/wolf_hirschhorn_syndrome_rare_genetic_disease.htm

Cromosoma 5 Cri du chat http://rarediseases.about.com/cs/criduchatsynd/a/010704.htm http://en.wikipedia.org/wiki/Cri_du_chat http://www.cafamily.org.uk/Direct/c81.html http://emedicine.medscape.com/article/942897-overview Displasia diastrofica Linfoma de clulas grandes anaplsticas http://en.wikipedia.org/wiki/Anaplastic_large_cell_lymphoma http://www.lymphomainfo.net/nhl/types/alcl.html

Cromosoma 7 Williams http://en.wikipedia.org/wiki/Williams_syndrome Cromosoma 9 Sindroma de Alfi http://en.wikipedia.org/wiki/Trisomy_9 Warkany http://en.wikipedia.org/wiki/Warkany_syndrome_2 Cromosoma 10 http://home.comcast.net/~daryl59/10q/ Cromosoma 11 Denys- Drash Jacobsen http://en.wikipedia.org/wiki/Jacobsen_syndrome Cromosoma 12 Darier Cromosoma 13 Patau http://en.wikipedia.org/wiki/Patau_syndrome http://www.wrongdiagnosis.com/p/patau_syndrome/prevalence.htm http://livingwithtrisomy13.org/ http://rarediseases.about.com/od/rarediseasesp/a/patau05.htm http://ghr.nlm.nih.gov/condition=trisomy13

Cromosoma 15 Angelman http://rarediseases.about.com/od/rarediseasesa/a/angelman05.htm http://en.wikipedia.org/wiki/Angelman_syndrome http://www.geneclinics.org/profiles/angelman/details.html

Prader-Willi http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176270 http://www.nlm.nih.gov/medlineplus/praderwillisyndrome.html http://en.wikipedia.org/wiki/Prader-Willi_syndrome http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pws http://pwsa.co.uk/main.php?catagory=1 http://rarediseases.about.com/od/rarediseasesp/a/praderwilli.htm

Cromosoma 16 http://rarediseases.about.com/od/chrosomedisorders/a/082104.htm http://www.trisomy16.org/ Cromosoma 17 Cistinose nefropatica Miller- Dieker http://en.wikipedia.org/wiki/Miller-Dieker_syndrome Smith-Magenies http://www.kumc.edu/gec/support/smith-ma.html http://en.wikipedia.org/wiki/Smith-Magenis_Syndrome http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sms http://membres.lycos.fr/asm17france/ Cromosoma 18 Edwards http://en.wikipedia.org/wiki/Edwards_syndrome http://www.trisomy18.org/site/PageServer http://rarediseases.about.com/cs/chromosome18/a/050104.htm Sindroma 18q Cromosoma 20 Cromosoma 20 nem anel http://www.epilepsy.com/epilepsy/epilepsy_ringchromosome Cromosoma 21

Down http://www.mayoclinic.com/health/down-syndrome/DS00182 http://www.nlm.nih.gov/medlineplus/downsyndrome.html http://en.wikipedia.org/wiki/Down_syndrome http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#TheOccurrence http://health.yahoo.com/children-genetic/down-syndrome-exams-and-tests/healthwise-hw167989.html http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2267988 http://www.undiag.com/diseases/downsyndrome.php http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm#DownSyndrome Cocana na gravidez http://www.otispregnancy.org/pdf/cocaine.pdf Despiste pr-natal do Down

http://www.ds-health.com/prenatal.htm http://www.healthfinder.gov/scripts/SearchContext.asp?topic=254 Down em mosaico http://www.ds-health.com/mosaic.htm Cromosoma 22 Coloboma da ris (cat eye) http://rarediseases.about.com/od/chromosomedisorders/a/cateyesyndrome.htm http://en.wikipedia.org/wiki/Cat_eye_syndrome Deleco 22.q11.2 http://ghr.nlm.nih.gov/condition=22q112deletionsyndrome http://en.wikipedia.org/wiki/CATCH_22_syndrome http://rarediseases.about.com/cs/digeorgesyndrome/a/080903.htm http://en.wikipedia.org/wiki/22q11.2_deletion_syndrome http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?requestURI=/healthatoz /Atoz/ency/digeorge_syndrome.jsp http://www.mayoclinic.com/health/digeorge-syndrome/DS00998 http://www.info4pi.org/patienttopatient/index.cfm?section=patienttopatient&content=syndromes&ar ea=3 http://emedicine.medscape.com/article/135711-overview Cromosoma X Agamaglobulinemia ligada ao X

http://en.wikipedia.org/wiki/X-linked_agammaglobulinemia Ausncia do X Noonan http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163950 Turner Dent X frgil

http://www.labcorp.com/pdf/Fragile_X_Syndrome_Patient_Brochure.pdf http://www.healthynj.org/dis-con/xchromosome/main.htm http://www.nlm.nih.gov/medlineplus/fragilexsyndrome.html http://www.healthfinder.gov/scripts/SearchContext.asp?topic=329 http://en.wikipedia.org/wiki/Fragile_X_syndrome_type_1 http://www.cdc.gov/ncbddd/single_gene/fragilex.htm http://www.fraxa.org/aboutfx.aspx http://www.fragilex.org/html/home.shtml http://www.uchsc.edu/fragilex/ FMR-1 e X- frgil http://www.cdc.gov/genomics/hugenet/factsheets/FS_FragileX.htm http://www.geneclinics.org/profiles/fragilex/ http://ghr.nlm.nih.gov/condition=fragilexsyndrome http://en.wikipedia.org/wiki/Xeroderma_Pigmentosum http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fragilex Sindroma linfoproliferativo ligado ao X Tratamento do X- frgil
http://www.fpg.unc.edu/~fx/Pages/edtreat.htm

Turner http://en.wikipedia.org/wiki/Turner_syndrome http://www.turner-syndrome.com/articles/turner-syndrome-symptoms/index.php http://turners.nichd.nih.gov/ http://www.magicfoundation.org/www/docs/115/turner_syndrome.html/ http://rarediseases.about.com/cs/turnersyndrome/a/020803.htm

Cromosoma XXY Klinefelter http://www.plasticsurgery4u.com/procedure_folder/male_breast4.html http://www.nlm.nih.gov/medlineplus/ency/article/000382.htm http://en.wikipedia.org/wiki/Klinefelter_syndrome http://www.klinefeltersyndrome.us/ http://emedicine.medscape.com/article/945649-overview Cromosoma Filadelfia Leucemia mieloide crnica Cromosoma XYY http://en.wikipedia.org/wiki/47,XYY_syndrome Cromosoma Y Deleco do cromosoma Y http://en.wikipedia.org/wiki/Y_chromosome_deletions Disomia uniparental http://ghr.nlm.nih.gov/handbook/inheritance/updimprinting http://en.wikipedia.org/wiki/Uniparental_disomy_of_11 http://www.medgen.ubc.ca/robinsonlab/mosaic/contents.htm http://www.wrongdiagnosis.com/c/chromosome_16_uniparental_disomy/intro.htm http://atlasgeneticsoncology.org/Deep/UniparentDisomyID20046.html http://jmg.bmj.com/cgi/content/full/45/9/545

Angelman Prader-Wili Russell-Silver Triplo A http://en.wikipedia.org/wiki/Triple_A_syndrome Triploidia http://en.wikipedia.org/wiki/Triploid_Syndrome Triplo X (trisomia X) http://en.wikipedia.org/wiki/Triplo_X_Syndrome http://ghr.nlm.nih.gov/condition=triplexsyndrome

http://www.aaa.dk/TURNER/ENGELSK/TRIPLEX.HTM

Idicentrico 15 http://en.wikipedia.org/wiki/Isodicentric_15

Nuclolos

So estruturas densas que se observam no ncleo apenas na interfase (perodo entre as divises celulares) Sintetizam trs das quatro molculas de rRNA que iro formar os ribossomas (28S, 18S e 5,8S) Estes rRNA so sintetizados pela RNA polimerase I e depois exportados para os ribosomas Importao e exportao do ncleo Importao Todas as protenas so sintetizadas no citosol e tm que ser importadas para o ncleo So histonas, protenas ribosmicas, factores de transcrio e de splicing Cada uma destas protenas exige uma sequncia particular de aminocidos selectiva para a sua entrada a sequncia de localizao nuclear (NLS)

Exportao As subunidades ribosomicas, mRNA, tRNA e factores de transcrio tm que sair do ncleo Estas protenas contm a sequncia de exportao nuclear (NES) que permite o seu reconhecimento para o transporte

http://www.web-books.com/MoBio/Free/Ch5B3.htm

http://en.wikipedia.org/wiki/Cell_nucleus Fig. 3.12 Importao e exportao do ncleo