biologi molekuler
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BIOLOGI MOLEKULER PROF. DR. M. KUSWANDI, APT BIOLOGI MOLEKULER I. Pengenalan Biologi Molekuler II. Materi Genetik Struktur dan Sifat Asam Nukleat Replikasi DNA, Mutasi dan Repair DNA III. Ekspresi Gena Transkripsi, Translasi, dan Regulasi IV. Pertumbuhan Sel Eukariot Sel Signaling dan Siklus Sel V. Transformasi Genetik Rekombinasi, Transposon dan Retrovirus III. DAFTAR PUSTAKA Lodish, H., Berk, A., Zipursky, A.L., Matsudaira, P., Baltimore, D., Darnell, J., 2000, Molecular cell Biology, 4th ed., Freeman and Company, New York. Alberts,B., Bray, D., Lewis, J., Raff, M., Robert, K., Watson, JD., 1994, Molecular Biology of the Cell, 3th ed.,Garland Publishing, Inc, New York. Devlin T.M., 2002, Biochemistry with Clinical Correlations, 5th ed., wiley-Liss, New York. Berg, J.M., Tymoczko, J.L., Stryer.,2002, Biochemistry, 5th ed.,W.H. Freeman and Company, New York. Freifelder, D.,1987, Molecular Biology, 2th ed., Jones and Bartlett Publisher, Boston. Glick, B.R. and Pasternak, J.J., 1998, Molecular Biotechnology, Principles and Applications of Recombinant DNA, 2nd. Ed. ASM Press, Washington DC. Brown, T.A., 2001, Gene Cloning and DNA Analysis, An Introduction, 4th ed., Blackwell Science, UK SISTEM EVALUASI UJIAN TENGAH SEMESTER UJIAN AKHIR SEMESTER – – – – – A B C D E > 75 65 – 74 55 – 64 35 – 54 <34 – MENGULANG BISA MEMPEROLEH A Human 2.9x109 bp 46 (Berg JM et al, 2002) REKAYASA GENETIK TEKNOLOGI GENA FARMASETIK PERBEDAAN PROKARIOT & EUKARIOT Prokariot Eukariot Organisme Bakteria dan sianobakteria Fungi, hewan, manusia Ukuran sel 1 - 10m 5 - 100m Organel Beberapa / tidak ada Inti, mitokondria, kloroplast GENOM Sirkuler dalam sitoplasma, Satu molekul kromosom Linier panjang, dipak rapi dgn protein histon dalam inti. Manusia mempunyai 46 cromosom RNA dan protein Disintesis dalam sitoplasma RNA : dalam inti, Protein: dalam sitoplasma Organisasi Unisel Multisel DNA mRNA mRNA RNAses IFs, EF, RF Translation Regulatory factors Proteins Decay Turnover Localization Interactions Modification Pre-mRNA Capping Polyadenylation Splicing mRNA Storage mRNA RNAses eIFs, eEF, eRF Translation Regulatory factors Proteins Decay Turnover Localization Interactions Modification (PO4/dPO4, glycosylation) II. MATERI GENETIK Mahluk hidup tersusun dari SEL yang dapat membelah dan menurunkan INFORMASI GENETIK nya Dibawa oleh DNA : rantai polimer panjang yang merupakan rangkaian dari jutaan nukleotida Fragmen DNA yang mengkode protein, suatu unit keturunan Gena Molekul DNA yang terdiri dari beberapa gena di paking membentuk CHROMOSOM Total informasi genetik yang tersimpan dalam kromosom GENOM What Is Cloning? A clone is a genetically identical copy of a living organism, such as the famous sheep ‘Dolly’ Similar to an identical twin TheCloning Making of Dolly depends on DNA Step 1: Take the Nuclei out of a sheep egg Step 2: Transfer nuclei from the Mother Empty DNA DNA Sheep Egg Mother’s Egg Hello Dolly July 5, 1996, Dolly was born at the Roslin Institute, Edinburgh, Scotland She was cloned using a cell taken from a healthy six-year-old sheep Cloning and the Cell Nucleus Its all about DNA Cloning Depends on DNA Nucleus Chromosome Good-Bye Dolly At age 3 Dolly showed signs of premature aging. Dolly died at 6 years old from progressive lung disease (symptom of old age) Dolly’s DNA was already 6 years old when she was born - WHY? It’s all about DNA Telomeres Telomeres TTAGGG Gene 1 Gene 2 Chromosome DNA Telomere Length Declines 8,000 Telomere length in base pairs (human white blood cells) 3,000 1,500 0 35 65 Age (years) More on Dolly and Cloning Dolly’s experimenters used 277 cloned embryos to produce one sheep, meaning 276 failed. Question How many failures will it take to produce a human Other Cloned Animals July 1998 cloned calves Cloned mouse Cloned mule Future Experiments ButterCat CatCow Future Experiments SparrowBoxer TigerOwl JUMLAH BASA VS KOMPLEKS MAKHLUK Chromosomes 16 6 24 Chromosomes 78 40 46 Maps of the genome Cytogenetic – For humans, known as a karyotype – Banding patterns are useful for identifying general regions of chromosome which might be altered in specific individuals – Fluorescent in situ hybridization (FISH) improves this resolution in some instances Linkage – Principal: genes or markers which are physically close to one another tend to travel together through meiosis – Linkage maps are recombination maps, and thus are relative, not absolute – Units of measurement: 1 cM = 1% recombination 1 cM ≈ 1 Mb = 1000 kB = 106 bp Banded chromosomes Maps of the genome Physical – Based on the actual physical location (in base pairs) of genes and markers – The initial physical maps were based on the analysis of somatic cell hybrids, in which human and animal cells were fused, then expressed genes were correlated with specific chromosomes which were retained in the hybrid as human chromsomes began to be extruded – The next phase involved construction of radiation hybrids, in which chromosomes are fragmented by radiation, then hybrids developed and analyzed as above – Current tools are cosmids, YACs, & BACs, which are interrogated with probes, then sequenced – Units of measurement: base pairs, kb, Mb; 3300 Mb total Relationship of physical & genetic maps Maps of the genome Homology – Comparison between species: to date, a humanmouse homology map has been completed, and the human-rat homology map is in process – Genomic resources for many other mammals now being constructed – Extremely useful for studies of gene function and for fine-grained study of regulatory sequences, both conserved and not Sequence map: the ultimate physical map – Approximately 85% of human genome now annotated HUMAN GENOME NUCLEAR GENOME * 23 pairs of chromosomes 2 X ( 3 X 109 b.p) 2 meters DNA / Cell * 2 X ( 3 X 1012 ) meters DNA in human body 8,000 X (earth to moon) MITOCHONDRIAL GENOME Human Genome Genome inti 23 pasang kromosome 2x (4x109 bp) 2m DNA/sel Genome mitokondria Some organisms are diploid - that is, they have paired homologous chromosomes in their somatic cells, and thus contain two copies of each gene. An organism in which both copies of the gene are identical - that is, have the same allele - is said to be homozygous for that gene. An organism which has two different alleles of the gene is said to be heterozygous Human 4 x 109 22 autosom yang berbeda 2 sex kromosom Masing2 single linier DNA E. Coli 4.7 x 106 1 Chromosom 40 – 50 loop superkoil Kromosom tanpa histon DNA CHROMOSOME KROMOSOM CENTROMER region dari chromosom yang diperlukan untuk pengikatan mitotic spindle saat proses mitosis TELOMER fragmen di ujung chromosom linier replikasi secara khusus untuk mencegah perpendekan chromosom ORIGIN REPLIKASI tempat awal replikasi berlangsung Introduction The Central Dogma of Molecular Biology Cell Transcription Reverse tanscription DNA mRNA Translation Ribosome Polypeptide (protein) KOMPOSISI GENA FUNGSIONAL PROMOTER OPERATOR ACTIVATOR BINDING SITE STRUKTURAL GEN : mRNA TERMINATOR
