ADN: REPLICACIN, REPARACIN Y RECOMBINACIN

ADN: REPLICACIN, REPARACIN Y RECOMBINACIN

1.- The Maintenance of DNA Sequences 2.- DNA Replication Mechanisms 3.- The Initiation and Completion of DNA Replication in Chromosomes 4.- DNA Repair

5.- General Recombination 6.- Site-Specific Recombination

1.- The Maintenance of DNA Sequences

Many Mutations in Proteins Are Deleterious and Are Eliminated by Natural Selection

Different proteins evolve at very different rates A comparison of the rates of amino acid change found in hemoglobin, histone H4, cytochrome c , and the fibrinopeptides.

2.- DNA Replication Mechanisms

Base-Pairing Underlies DNA Replication and DNA Repair

The DNA double helix acts as a template for its own duplication Because the nucleotide A will successfully pair only with T, and G only with C, each strand of DNA can serve as a template to specify the sequence of nucleotides in itscomplementary strand by DNA base-pairing. In this way, a double-helical DNA molecule can be copied precisely.

The chemistry of DNA synthesis The addition of a deoxyribonucleotide to the 3 end of a polynucleotide chain (the primer strand) is the fundamental reaction by which DNA is synthesized. As shown,basepairing between an incoming deoxyribonucleoside triphosphate and an existing strand of DNA (the template strand) guides the formation of the new strand of DNA and causes it to have a complementary nucleotide sequence.

DNA synthesis catalyzed by DNA polymerase (A) As indicated, DNA polymerase catalyzes the stepwise addition of a deoxyribonucleotide to the 3OH end of a polynucleotide chain, the primer strand, that is paired to a second template strand. (B) The structure of an E. coli DNA polymerase molecule,

The DNA Replication Fork Is Asymmetrical

The semiconservative nature of DNA replication In a round of replication, each of the two strands of DNA is used as a template for the formation of a complementary DNA strand. The original strands therefore remain intact through many cell generations.

The structure of a DNA replication fork Because both daughter DNA strands are polymerized in the 5-to-3 direction, the DNA synthesized on the lagging strand must be made initially as a series of short DNA molecules, called Okazaki fragments.

The High Fidelity of DNA Replication Requires Several Proofreading Mechanisms

Editing by DNA polymerase Outline of the structures of DNA polymerase complexed with the DNA template in the polymerizing mode (left) and the editing mode (right). The catalytic site for the exonucleolytic (E) and the polymerization (P) reactions are indicated

RNA primer synthesis A schematic view of the reaction catalyzed by DNA primase, the enzyme that synthesizes the short RNA primers made on the lagging strand using DNA as a template.

An assay used to test for DNA helicase enzymes A short DNA fragment is annealed to a long DNA single strand to form a region of DNA double helix. The double helix is melted as the helicase runs along the DNA single strand, releasing the short DNA fragment in a reaction that requires the presence of both the helicase protein and ATP.

Regin de 1 sola cadena de DNA presentando regiones cortas por apareamiento de las bases

Efecto de las protenas que se unen a una sola herba sobre la estructura del DNA de 1 sola hebra.

The proteins at a bacterial DNA replication fork The major types of proteins that act at a DNA replication fork are illustrated, showing their approximate positions on the DNA.

Horquila de replicacion de DNA en 3D

3.- The Initiation and Completion of DNA Replication in Chromosomes

A replication bubble formed by replication fork initiation This diagram outlines the major steps involved in the initiation of replication forks at replication origins. The structure formed at the last step, in which both strands of the parental DNA helix have been separated from each other and serve as templates for DNA synthesis

The four successive phases of a standard eucaryotic cell cycle During the G1, S, and G2 phases, the cell grows continuously. During M phase growth stops, the nucleus divides, and the cell divides in two. DNA replication is confined to the part of interphase known as S phase. G1 is the gap between M phase and S phase; G2 is the gap between S phase and M phase.

Different regions of a chromosome are replicated at different times in S phase These light micrographs show stained mitotic chromosomes in which the replicating DNA has been differentially labeled during different defined intervals of the preceding S phase.

The structure of telomerase The telomerase is a proteinRNA complex that carries an RNA template for synthesizing a repeating, G-rich telomere DNA sequence. Only the part of the telomerase protein homologous to reverse transcriptase is shown here (green). A reverse transcriptase is a special form of polymerase enzyme that uses an RNA template to make a DNA strand; telomerase is unique in carrying its own RNA template with it at all times.

4.- DNA Repair

A summary of spontaneous alterations likely to require DNA repair

Spontaneous oxidative damage (red arrows)

Hydrolytic attack (blue arrows) Uncontrolled methylation by the methyl group donor Sadenosylmethionine (green arrows)

Depurination and deamination These two reactions are the most frequent spontaneous chemical reactions known to create serious DNA damage in cells. Depurination can release guanine (shown here), as well as adenine, from DNA. The major type of deamination reaction (shown here) converts cytosine to an altered DNA base, uracil, but deamination occurs on other bases as well. These reactions take place on double-helical DNA

The thymine dimer This type of damage is introduced into DNA in cells that are exposed to ultraviolet irradiation (as in sunlight). A similar dimer will form between any two neighboring pyrimidine bases (C or T residues) in DNA.

The recognition of an unusual nucleotide in DNA by base-flipping The DNA glycosylase family of enzymes recognizes specific bases in the conformation shown. Each of these enzymes cleaves the glycosyl bond that connects a particular recognized base (yellow) to the backbone sugar, removing it from the DNA.

5.- General Recombination

General recombination The breaking and rejoining of two homologous DNA double helices creates two DNA molecules that have crossed over. In meiosis, this process causes each chromosomein a germ cell to contain a mixture of maternally and paternally inherited genes.

A heteroduplex joint This structure unites two DNA molecules where they have crossed over. Such a joint is often thousands of nucleotides long.

General Recombination Can Cause Gene Conversion

6.- Site-Specific Recombination

structure of the enzyme from HIV