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Pendahuluan Biologi Molekuler. Mathematical Biosciences Institute (Ohio State Univ), 2 October 2003 RNA Protein DNA DOGMA CENTRAL.

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Presentasi berjudul: "Pendahuluan Biologi Molekuler. Mathematical Biosciences Institute (Ohio State Univ), 2 October 2003 RNA Protein DNA DOGMA CENTRAL."— Transcript presentasi:

1 Pendahuluan Biologi Molekuler

2 Mathematical Biosciences Institute (Ohio State Univ), 2 October 2003 RNA Protein DNA DOGMA CENTRAL

3 Dogma central Biologi Molekuler Adapted from DNA Sequence (splited by genes) RNA fenotip protein Asam amino

4 DNA Fosfat Basa (A,T, C or G) Gula DNA adalah komponen yang tersusun dari dari molekul-molekul yang disebut nukleotid Masing-masing nukleotid mengandung fosfat, gula dan basa nitrogen. Ada empat basa: Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)

5 DNA: structure Ikatan gula-fosfat pada nukleotid merupakan backbone dari ikatan pada DNA Empat basa dari DNA dibentuk sepanjang “backbone” disebut dengan DNA sequence. Dua DNA saling berikatan di antara pasangan basa Dua ikatan basa yang mungkin yaitu: A-T, C-G. Dua untai DNA mempunyai formasi struktur double helixTwo. Source of diagram:

6 DNA: tersusun dalam kromosom Each chromosome is essentially a package for a very long, continuous DNA double strand. Each chromosome is essentially a package for a very long, continuous DNA double strand. Lodish et al. Molecular Biology of the Cell (5 th ed.). W.H. Freeman & Co., 2003.

7 DNA: di-splid oleh gen-gen gene promoterExon 1 Exon 2 Exon 3 Intron 1 Intron 2 Gen merupakan bagian dari DNA yang membawa informasi untuk membentuk protein. 2-3% dari DNA manusia adalah gen, gen yang tidak aktif (rest) disebut junk DNA Promotor terlelak di bagian awal dari komponen gen. Promotor aktif saat gen akan bekerja. Pada banyak gen euryotic, gen adalahsekuen DNA yang mempunyai kode, yang juga disebut sebagai exon. Bagian yang tidak membawa kode genetik disebut sebagai intron.

8 RNA Source of diagram: RNA (ribonucleic acid) adalah intermediet antara DNA dan protein. RNA merupakan single strand dari asam nukleat. Basa nitrogen T (Thymine) pada RNA terganti oleh U (Uracil) Tidak seperti DNA, yang terlokasi di inti, RNA juga dapat ditemukan di sitoplasma. Pada inti, kode gen ditranskripsikan pada RNA. Selanjutnya RNA akan keluar dari inti ke nukleus dalam sitoplasma, dimana RNA ditranslasi menjadi asam amino.

9 Another view of central dogma Gen diekspresikan pada 3 step: 1) Transkripsi: Sintesis RNA 2) Splicing: penghilangan intron dari RNA 3) Translasi: Sintesis Protein

10 Transkripsi Transkripsi diinisiasi oleh kompleks dari faktor=faktor transkripsi yang berikatan dengan promotor. An enzyme, RNA polymerase II, travels along the gradually unzipped DNA template and polymerizes nucleotides into an RNA. The sequence of nucleotides on DNA template determines the sequence on RNA by following the rule of base-pair complementarity, i.e., A – U, T- A, C – G, G – C. Transcription continues until entire gene is copied to RNA. Source of diagram: Animation

11 Splicing pre mRNA Exon 1 Exon 2 Exon 3 Intron 1 Intron 2 mature mRNA

12 Translation (1) By translation, the nucleotide sequence on mRNA determines the amino acid sequence by genetic code. Genetic code: three base pairs of RNA (called a codon) determine one amino acid based on a fixed table. Translation always starts at AUG (start codon), and ends with any of UAA, UAG, or UGA (stop codon)

13 Translation (2) Transfer RNAs (tRNAs): small RNA molecules. Most of the tRNAs function as carriers of amino acids and participate in protein synthesis. Transfer RNAs (tRNAs): small RNA molecules. Most of the tRNAs function as carriers of amino acids and participate in protein synthesis. For example, the tRNA with the anticodon CGG corresponds with the codon GCC and attaches alanine amino acid onto the peptide chain. For example, the tRNA with the anticodon CGG corresponds with the codon GCC and attaches alanine amino acid onto the peptide chain. Ribosome: a complex of protein and rRNA Ribosome: a complex of protein and rRNA Animation Source of diagram:

14 Summary Central dogma of molecular biology Central dogma of molecular biology Three components Three components DNA DNA RNA RNA Protein Protein Three steps Three steps transcription transcription splicing splicing translation translation

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16 Cell – cell communication

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18 Proto- oncogenes encode components of growth factor signal transduction pathways Components shown in yellow are known proto- oncogenes

19 The VEGF family and its receptors Adapted from Ferrara N. Nat Med 2003;9:669–76 Migration, permeability, DNA synthesis, survival Lymphangiogenesis – P P– – P P– – P P– VEGF-A VEGF-B PlGF VEGF receptor-1 VEGF-A VEGF receptor-2 VEGF-C VEGF-D VEGF receptor-3 Angiogenesis

20 VEGF signal transduction and its effects Shibuya M. Cell Struct Funct 2001;26:25–35 VEGF binding to VEGF receptor-2 activates a signalling cascade resulting in cellular effects Cation channel  Permeability – P P– – P P– – P P– VEGF VEGF receptor-1 VEGF VEGF receptor-2 VEGF-C VEGF-D VEGF receptor-3 DAG PLC Protein kinase C Raf-1 MAPK Proliferation, migration  Permeability SAPK/ JNK Apoptosis Survival Calcium release Ca 2+ Proliferation Migration IP 3 PLC P13K Protein kinase B

21 Agents targeting the VEGF pathway VEGF VEGF receptor-2 Cation channel  Permeability Antibodies inhibiting VEGF (e.g. bevacizumab) Antibodies inhibiting VEGF receptors Soluble VEGF receptors (VEGF-TRAP) Small-molecules inhibiting VEGF receptors (TKIs) (e.g. PTK-787) Ribozymes (Angiozyme) – P P– – P P– – P P– Migration, permeability, DNA synthesis, survival Lymphangiogenesis Angiogenesis

22 GDP Sos Grb2 PP GTP Ras Growth factor P120-GAP Neurofibromin Inactive Raf Transcription factors etc. DNA synthesis Nucleus MEK ERK1 ? Active Raf P13-K Rac and Rho pathway Morphological change Ras Signal Transduction from Receptor to Nucleus Via RAS p21

23 Regulators : proliferation, differentiation, apoptosis, repair Genome : Genome : Genes : Genes : Cell cycle Cell cycle Differentiatio Differentiatio Apoptosis Apoptosis Repair Repair Metabolism Metabolism etc etc Proteome Proteome Protein: Protein: cyclin, CDK,CDKI cyclin, CDK,CDKI GF : GM-CSF, FGF GF : GM-CSF, FGF Bcl-2, p53, caspase Bcl-2, p53, caspase Gadd, enzym repair Gadd, enzym repair dll dll Transcriptome RNA


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