BIOLOGI MOLEKULERPengenalan Biologi MolekulerMateri GenetikStruktur dan Sifat Asam NukleatReplikasi DNA, Mutasi dan Repair DNAIII. Ekspresi GenaTranskripsi, Translasi, dan RegulasiIV. Pertumbuhan Sel EukariotSel Signaling dan Siklus SelV. Transformasi GenetikRekombinasi, 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 EVALUASIUJIAN TENGAH SEMESTERUJIAN AKHIR SEMESTERA > 75B 65 74C55 64D35 54E

(Berg JM et al, 2002)Human 2.9x109 bp

REKAYASA GENETIKTEKNOLOGI GENA FARMASETIK

PERBEDAAN PROKARIOT & EUKARIOT

ProkariotEukariotOrganismeBakteria dan sianobakteriaFungi, hewan, manusiaUkuran sel1 - 10m5 - 100mOrganelBeberapa / tidak adaInti, mitokondria, kloroplastGENOMSirkuler dalam sitoplasma,Satu molekul kromosomLinier panjang, dipak rapi dgn protein histon dalam inti.Manusia mempunyai 46 cromosomRNA dan proteinDisintesis dalam sitoplasmaRNA : dalam inti, Protein: dalam sitoplasmaOrganisasiUniselMultisel

mRNATranslationRNAsesDecayProteinsTurnoverInteractionsModificationRegulatory factorsLocalizationDNAmRNAIFs, EF, RF

mRNAStorageTranslationRNAsesDecayProteinsTurnoverInteractionsModification(PO4/dPO4, glycosylation)Regulatory factorsLocalizationPre-mRNACappingPolyadenylationSplicingmRNAeIFs, eEF, eRF

II. MATERI GENETIKMahluk hidup tersusun dari SELyang dapat membelah dan menurunkan INFORMASI GENETIK nya Dibawa oleh DNA : rantai polimer panjang yang merupakan rangkaian dari jutaan nukleotida Molekul DNA yang terdiri dari beberapa gena di paking membentuk CHROMOSOM Total informasi genetik yang tersimpan dalam kromosom GENOMFragmen DNA yang mengkode protein, suatu unit keturunan Gena

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

The Making of DollyCloning depends on DNAStep 1: Take the Nuclei out of a sheep eggStep 2: Transfer nuclei from the MotherSheep EggMothers Egg

Hello DollyShe was cloned using a cell taken from a healthy six-year-old sheep July 5, 1996, Dolly was born at the Roslin Institute, Edinburgh, Scotland

Cloning and the CellNucleusIts all about DNA

Cloning Depends on DNAChromosome

Good-Bye DollyDollys DNA was already 6 years old when she was born - WHY?At age 3 Dolly showed signs of premature aging.Dolly died at 6 years old from progressive lung disease (symptom of old age)

TelomeresChromosomeTelomeres

Telomere Length DeclinesTelomere length in base pairs(human white blood cells)

More on Dolly and CloningHow many failures will it take to produce a human Dollys experimenters used 277 cloned embryos to produce one sheep, meaning 276 failed. Question

Other Cloned Animals

Future Experiments

Future Experiments

JUMLAH BASA VS KOMPLEKS MAKHLUK

Chromosomes16624

Chromosomes784046

Maps of the genomeCytogeneticFor humans, known as a karyotypeBanding patterns are useful for identifying general regions of chromosome which might be altered in specific individualsFluorescent in situ hybridization (FISH) improves this resolution in some instancesLinkagePrincipal: genes or markers which are physically close to one another tend to travel together through meiosisLinkage maps are recombination maps, and thus are relative, not absoluteUnits of measurement: 1 cM = 1% recombination 1 cM 1 Mb = 1000 kB = 106 bp

Banded chromosomes

Maps of the genomePhysicalBased on the actual physical location (in base pairs) of genes and markersThe 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 extrudedThe next phase involved construction of radiation hybrids, in which chromosomes are fragmented by radiation, then hybrids developed and analyzed as aboveCurrent tools are cosmids, YACs, & BACs, which are interrogated with probes, then sequencedUnits of measurement: base pairs, kb, Mb; 3300 Mb total

Relationship of physical & genetic maps

Maps of the genomeHomologyComparison between species: to date, a human-mouse homology map has been completed, and the human-rat homology map is in processGenomic resources for many other mammals now being constructedExtremely useful for studies of gene function and for fine-grained study of regulatory sequences, both conserved and notSequence map: the ultimate physical mapApproximately 85% of human genome now annotated

HUMAN GENOMENUCLEAR 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 GenomeGenome inti 23 pasang kromosome 2x (4x109 bp) 2 m DNA/selGenome 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

E. Coli 4.7 x 106 1 Chromosom40 50 loop superkoilHuman 4 x 109 22 autosom yang berbeda 2 sex kromosomMasing2 single linier DNA

DNACHROMOSOME

KROMOSOMCENTROMERregion dari chromosom yang diperlukan untuk pengikatan mitotic spindle saat proses mitosisTELOMER fragmen di ujung chromosom linier replikasi secara khusus untuk mencegah perpendekan chromosom ORIGIN REPLIKASItempat awal replikasi berlangsung

IntroductionThe Central Dogma of Molecular BiologyCell

KOMPOSISI GENA FUNGSIONALPROMOTEROPERATORACTIVATOR BINDING SITESTRUKTURAL GEN : mRNATERMINATOR

human clones are never absolutely identical to the original; for example, so-called identical human twins, while clones, are still two different people who possess their own separate souls The mother is to be cloned since her DNA was usedIn cloning we are interested in the Nucleus (DNA)Each cell contains DNA. DNA is packaged into compact units called chromosomes.Basically a chromosome is one long chain of genetic material. It is the microscopic, rod-shaped, threadlike part of the cell that carries hereditary information in the form of genes. Every cell has chromosomes and all individuals in the same species have the same number of chromosomes. Within an individual, every cell has the same number of chromosomes and generally come in pairs (except in sex cells).

People with Down Syndrome have 3 copies of chromosome 21.telomeres, these molecular chains have often been compared to the blank leaders on film and recording tape. Indeed, telomeres seem to perform a similar function in aligning the DNA molecule during the replication process. Protecting the vital DNA molecule from being copied out of synch, these telomeres provide a kind of buffer zone where asynchronous replication errors (that are inevitable) will not result in any of the vital DNA sequences being lost. As a cell gets older, it is under attack by oxides and other so-called free-radical chemicals in the body and environment. We survive as living beings because our cells have the ability to duplicate themselves before being killed by these natural causes. Each time our cells duplicate themselves, a small portion of the DNA molecule is lost and not copied. The loss is usually to the telomere and so the effect is usually insignificant.Scientists recently noted that the length of these telomere chains were shorter as we grew older. Eventually, the telomeres become so shortened that the losses in replication begin to effect the vital DNA molecule sequence and prevent the cell from being able to duplicate itself. This is why we age.

Dollys birth was one of the biggest news stories of the nineties. Scientists made extravagant promises about medical and technological advances. Well, Dollys embarrassingly premature death received little attention, precisely because it exposes the horrors of cloning. Dolly was diagnosed with arthritis, normally found in old sheep

Telomeres are the ends of our chromosomes. Made of many repeats of the same DNA sequence, they act like shoelace caps: they protect the gene-containing body of the chromosome from being worn down. Breakdowns in telomere maintenance are implicated in ageing and cancer. Telomeres sit on the ends of chromosomes to protect them from damage. When chromosomes are replicated during cell division, a stretch of the telomere is left unreplicatedmaking the telomere a bit shorter with each division. After some 50 to 100 divisions, the telomeres become so short that the cell can no longer dividea phenomenon scientists call senescencethat is, the state of being old. TELOMERES in human beings are a repeating sequence of three of these nucleotide units: Thymine (T), Adenine (A), and Guanine (G), in the sequence:Important in replication - they act like a buffer zoneEach time a normal cell divides its telomeres are cut shorterCells with critically short telomeres become unable to divide further, and eventually malfunction and dieBasically a chromosome is one long chain of genetic material. It is the microscopic, rod-shaped, threadlike part of the cell that carries hereditary information in the form of genes. Every cell has chromosomes and all individuals in the same species have the same number of chromosomes. Within an individual, every cell has the same number of chromosomes and generally come in pairs (except in sex cells). Humans, for instance, have 23 pairs, or 46 chromosomes.A gene can be defined as a region of DNA that controls a hereditary characteristic. It usually corresponds to a sequence used in the production of a specific protein or RNA.Genes can be as short as 1000 base pairs or as long as several hundred thousand base pairs. It can even be carried by more than one chromosome. The estimate for the number of genes in humans has decreased as our knowledge has increased. As of 2001, humans are thought to have between 30,000 and 40,000 genes.telomere is a repeating DNA sequence (TTAGGG) at the end of the body's chromosomes. The telomere can reach a length of 15,000 base pairs. Telomeres function by preventing chromosomes from losing base pair sequences at their ends. They also stop chromosomes from fusing to each other. However, each time a cell divides, some of the telomere is lost (usually 25-200 base pairs per division). When the telomere becomes too short, the chromosome reaches a "critical length" and can no longer replicate. This means that a cell becomes "old" and dies by a process called apoptosis. Telomere activity is controlled by two mechanisms: erosion and addition. Erosion, as mentioned, occurs each time a cell divides. Addition is determined by the activity of telomerase. apoptosis: The process by which a cell dies at a natural, "pre-programmed" time

Telomere length declines in dividing cells as we age.In human blood cells, the length of telomeres ranges from 8,000 base pairs at birth to 3,000 base pairs as people age and as low as 1,500 in elderly people. (An entire chromosome has about 150 million base pairs.) Each time a cell divides, an average person loses 30 to 200 base pairs from the ends of that cells telomeres.Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent, die or sustain genetic damage that can cause cancer.Telomeres do not shorten with age in tissues such as heart muscle in which cells do not continually divide.

A telomere is a repeating DNA sequence (TTAGGG) at the end of the body's chromosomes. The telomere can reach a length of 15,000 base pairs. Telomeres function by preventing chromosomes from losing base pair sequences at their ends. They also stop chromosomes from fusing to each other. However, each time a cell divides, some of the telomere is lost (usually 25-200 base pairs per division). When the telomere becomes too short, the chromosome reaches a "critical length" and can no longer replicate. This means that a cell becomes "old" and dies by a process called apoptosis. Telomere activity is controlled by two mechanisms: erosion and addition. Erosion, as mentioned, occurs each time a cell divides. Addition is determined by the activity of telomerase. apoptosis: The process by which a cell dies at a natural, "pre-programmed" time