Dna and rna_molecular_biology_part3_dent_april_2nd_2012

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DNA/RNA…… part 3

By

Taghrid El Abaseri MD, PhD.

April 2nd 2012SCU Dentistry School D1

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The Replication Fork

Only one strand of DNA is synthesized in a continuous manner in the direction of overall DNA replication 5 to 3

The leading strand is the strand of DNA that is synthesized continuously in the direction of movement of the replication fork.

Okazaki fragments are small pieces of newly synthesized DNA that are joined to form an intact new DNA strand.

DNA ligase is an enzyme that seals breaks in DNA strands.

The lagging strand is the strand of DNA synthesized opposite to the direction of movement of the replication fork, by ligation of Okazaki fragments.

Short fragments of RNA serve as primers for DNA replication.

Primase is an enzyme that synthesizes short fragments of RNA complementary to the lagging strand template at the replication fork.

RNase H is an enzyme that degrades the RNA strand of RNA-DNA hybrids, and 5 to 3 exonucleases.

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Synthesis of leading and lagging strands of DNA

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Initiation of Okazaki fragments with RNA primers

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Removal of RNA primers and joining of Okazaki fragments

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Expression of Genetic Information

Genes act by determining the structure of proteins, which are responsible for directing cell metabolism through their activity as enzymes.

Proteins, in turn, are polymers of 20 amino acids, the sequence of which determines their structure and function.

The first direct link between a genetic mutation and an alteration in the amino acid sequence of a protein was made in 1957.

• Individuals with the inherited disease sickle-cell anemia have hemoglobin molecules that differ from normal ones by a single amino acid substitution.

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Colinearity of Genes and Proteins

The simplest hypothesis to account for the relationship between genes and enzymes was that the order of nucleotides in DNA specified the order of amino acids in a protein.

Another hypothesis predicted that different mutations within a single gene could alter different amino acids in the encoded protein.

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Synthesis of RNA from DNA

Although the sequence of nucleotides in DNA appeared to specify the order of amino acids in proteins, it did not necessarily follow that DNA itself directs protein synthesis.

RNA appeared a likely candidate for such an intermediate because the similarity of its structure to that of DNA suggested that RNA could be synthesized from a DNA template.

RNA polymerase is the principal enzyme responsible for RNA synthesis.

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Eukaryotic RNA Polymerases and General Transcription Factors

eukaryotic cells contain multiple different RNA polymerases that transcribe distinct classes of genes.

Transcription in eukaryotes takes place on chromatin rather than on free DNA.

Regulation of chromatin structure is an important factor in the transcriptional activity of eukaryotic genes.

Eukaryotic cells contain three distinct nuclear RNA polymerases that transcribe different classes of genes.

Although all three of the nuclear RNA polymerases recognize different promoters and transcribe distinct classes of genes, they share several features in common with each other

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Transcription in eukaryotes

A promoter is the DNA sequence to which RNA polymerase binds to initiate transcription of a gene.

After transcription stops, the RNA is released from the polymerase, and the enzyme dissociates from its DNA template.

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Transcription by RNA polymerase

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Processing of mRNA in Eukaryotes

Pre-mRNA is the primary transcript that is processed to form messenger RNA in eukaryotic cells.

A 7-methylguanosine cap is what is added during the modification of the 5end of a transcript.

A poly-A tail is a tract of about 200 adenine nucleotides added to the 3 ends of eukaryotic mRNAs.

Polyadenylation is the process of adding a poly-A tail to a pre-mRNA.

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Processing of eukaryotic messenger RNAs

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The Role of Messenger RNA

The central dogma of molecular biology states that RNA molecules are synthesized from DNA templates, and proteins are synthesized from RNA templates.

• Transcription is the synthesis of an RNA molecule from a DNA template.

• Translation is the synthesis of a polypeptide chain from an mRNA template.

Messenger RNAs (mRNAs) are RNA molecules that serve as templates for protein synthesis.

RNA polymerase is an enzyme that catalyzes the synthesis of RNA.

Ribosomal RNA (rRNA) is a component of ribosomes.

Transfer RNAs (tRNAs) serve as adaptor molecules that align amino acids along the mRNA template.

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The Genetic Code

Genetic information is transferred between nucleic acids and proteins.

The genetic code is the correspondence that takes place between nucleotide triplets and amino acids in proteins.

Codons are the basic units of the genetic code.

Function of transfer RNA

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Translation of mRNA

Proteins are synthesized from mRNA templates by a process that has been highly conserved throughout evolution.

Translation is carried out on ribosomes, with tRNAs serving as adaptors between the mRNA template and the amino acids being incorporated into protein.

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Structure of tRNAs

Transfer RNAs, or tRNAs, possess unique identifying sequences that allow the correct amino acid to be attached and aligned with the appropriate codon in mRNA.

Transfer RNAs are approximately 70 to 80 nucleotides long and have characteristic cloverleaf structures.

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Transfer RNAs

Aminoacyl tRNA synthetases are a group of enzymes that recognize a single amino acid, as well as the correct tRNA (or tRNAs) to which that amino acid should be attached.

After being attached to tRNA, an amino acid is aligned on the mRNA template by complementary base pairing between the mRNA codon and the anticodon of the tRNA.

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Ribosome structure

Like tRNAs, rRNAs form characteristic secondary structures by complementary base pairing.

The role of rRNA in the formation of peptide bonds extends the catalytic activities of RNA beyond self-replication to direct involvement in protein synthesis.

Ribosomes are the sites of protein synthesis in both prokaryotic and eukaryotic cells.

Ribosomal RNAs, or rRNAs, are the ribosomal components of ribosomes.

The general structures of prokaryotic and eukaryotic ribosomes are similar, although they differ in some details.

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The Organization of mRNAs and the Initiation of Translation

The signals that identify initiation codons in eukaryotic cells.

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Overview of translation

Translation is generally divided into three stages: initiation, elongation, and termination.

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Initiation of translation in eukaryotic cells

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Elongation stage of translation

After the initiation complex has formed, translation proceeds by elongation of the polypeptide chain.

Elongation factors, which are complexed to GTPs, escort the aminoacyl tRNA to the ribosome.

The next step in elongation is translocation, which requires another elongation factor and is coupled to GTP hydrolysis.

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Termination of translation

Release factors are proteins that recognize stop codons and terminate translation of mRNA.

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