01-dna structure.pdf
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01. DNA Structure and Organization
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Griffith – 1928 – Transformation experiments
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Hershey and Chase – 1952 - Transduction
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DNA is a polar polymer 5’ Ph43’ OH
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Informação adicional:
1. Densidade da molécula nativa muito alta
2. Decomposição da molécula nativa em nucleótidos resultava emque as proporções dos diferentes componentes eram sempre:
Guaninas = Citocinas Adeninas = Timinas
3. A molécula nativa tinha um diâmetro constante (20 Å)
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α β γ
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Estabilidade do DNA
Interações hidrofóbicas entre as basesque resultam na sua orientação principalmenteperpendicular ao eixo da molécula.
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Desnaturation e renaturation do DNA
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DNA melting curves
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Southern blotting
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Estrutura secundaria do DNA
Linear DNA molecule
Região de dupla simetria com sequenciasrepetidas invertidas
Positive supercoiling
Link number = 0
Link number = 3
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Nucleossoma
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Modelos da organização da cromatina
Bead on a string 11 nm
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Modelos da organização da cromatina
Solenoid 30 nm
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Remodelação da cromoatina
Dependente do ATP
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Diversas proteínas interatuam com o DNA
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C-terminal das histonas
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O Código epigenético
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O Código epigenético
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1
6-7
40
680
1.2 x 104
Packingratio
Organização do DNA nu núcleo
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Scaffold Matrix
Mitotic Interphase (nucleus)
The chromosome Scaffold
Remover DNA com nucleases e DNA com NaClProteínas não histonasTopoisomerase IIStructural Maintenance of Chromosomes SMCs
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Codensin is involved in the organization of mitotic chromosomes
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Cohesin maintains sister chromatids together from G1 to end of Mitosis
DNACondensinCohesin
Cornelia de Lange Syndrome
(1/10,000) severe developmental deffects
Mutations at SMC1/3 or SCC2 (chaperone of SCC1)
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Genoma de um organismoChromosome painting
1 N = Haploide2 N = Diploide
Control cancer cell
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Chromosome territories in human cells
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Gene localization changes within the nucleous in response to transcription
Genomics
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Genomics
DNA complexity
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DNA complexity
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25,000
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Tipos de sequencias no genoma
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Repeats Transpose Repeat
TE
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Transposons
Barbara McClintock 1902-1992
Nobel prize of Physiology and Medicine 1983
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Transposition
- Normalmente reprimida- Pode ser activada- Induz alterações em genes- Induz quebras cromossomicas
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Transposons
“copy paste via RNA or DNA”
Transposões podem inativar genes
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Transposões podem inativar genes
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Heterocromatina
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O Genoma humano
SINEs: Short Interspersed Nuclear Elements
- Short <500 b- Transcribed by RNA pol III- Non-coding- Alu sequences (280 bp) cut RE Alu- 1,5 M copies- Use TEs for mobilization
LINEs: Long Interspersed Nuclear Elements
- Heterogenous in lenght- Transcribed by RNA pol II- Code for reverse transcriptase and endonuclease- 500,000 copies- Move by coping so enlarge the genome
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