Bacterial Replication Error Rate

Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 ↵‡ To whom correspondence should be addressed. Tel.: 919-541-2644; Fax: 919-541-7613; E-mail: kunkel{at}niehs.nih.gov.  Next bacterial dna replication Section When describing the structure of the DNA double helix, Watson and Crick (1)

Bacterial Replication Animation

wrote, “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism

Bacterial Replication Video

for the genetic material.” Fifty years later, interest in the fidelity of DNA copying mechanisms remains high because the balance between correct and incorrect DNA synthesis is relevant to a great deal of

Bacterial Replication Fork And Its Principal Proteins

biology. High fidelity DNA synthesis is beneficial for maintaining genetic information over many generations and for avoiding mutations that can initiate and promote human diseases such as cancer and neurodegenerative diseases. Low fidelity DNA synthesis is beneficial for the evolution of species, for generating diversity leading to increased survival of viruses and microbes when subjected to changing environments, and for the development of a normal immune bacterial replication termination system. What was not yet appreciated 50 years ago was the large number and amazing diversity of transactions involving DNA synthesis required to faithfully replicate genomes and to stably maintain them in the face of constant challenges from cellular metabolism and the external environment. To perform these tasks, cells harbor multiple DNA polymerases (2, 3), many of which have only been discovered in the past 5 years and whose cellular functions are not fully understood. These polymerases differ in many features including their fidelity. This diversity and the sequence complexity of genomes provide the potential to vary DNA synthesis error rates over a wider range than was appreciated a few years ago. This article reviews major concepts and recent progress on DNA replication fidelity with additional perspectives found in longer reviews cited throughout. Previous SectionNext Section How Accurate Is DNA Synthesis? Studies of bacteriophage and Escherichia coli replication in the absence of DNA mismatch repair and external environmental stress suggest that the base substitution error rate of the replication machinery in vivo is in the range of 10–7 to 10–8 (4). Eukaryotic DNA replication is likely to be at least this accurate (5). High chromosomal replication fidelity i

the number of mutations that could accumulate in a population over time. A few pages ago we looked at the origin of antibiotic resistance in bacteria in order to prove that mutations occur randomly. bacterial replication bubble Now we'll consider just how frequency those mutations could arise in bacteria. Then we'll ask bacterial replication is accomplished primarily by how frequently mutations occur in humans. Our model bacterium is Esherichia coli the common, and mostly benign, intestinal bacterium. The entire genome bacterial replication transcription and translation was sequenced in 1997 (Blattner et al., 1997) and its size is 4,200,000 base pairs (4.2 × 106 bp). Every time a bacterium divides this amount of DNA has to be replicated; that's 8,400,000 nucleotides (8.4 × http://www.jbc.org/content/279/17/16895.full 106). The most common source of mutation is due to mistakes made during DNA replication when an incorrect nucleotide is incorporated into newly synthesized DNA. The mutation rate due to errors made by the DNA polymerase III replisome is one error for every one hundred million bases (nucleotides) that are incorporated into DNA. This is an error rate of 1/100,000,000, commonly written as 10-8 in exponential notation. Technically, these aren't mutations; they count as http://sandwalk.blogspot.com/2007/07/mutation-rates.html DNA damage until the problem with mismatched bases in the double-stranded DNA has been resolved. The DNA repair mechanism fixes 99% of this damage but 1% escapes repair and becomes a mutation. The error rate of repair is 10-2 so the overall error rate during DNA replication is 10-10 nucleotides per replication (10-8 × 10-2) (Tago et al., 2005). Since the overall mutation rate is lower than the size of the E. coli genome, on average there won't be any mistakes made when the cell divides into two daughter cells. That is, the DNA will usually be replicated error free. However, one error will occur for every 10 billion nucleotides (10-10) that are incorporated into DNA. This means one mutation, on average, every 1200 replications (8.4 × 106 × 1200 is about ten billion). This may not seem like much even if the average generation time of E. coli is 24 hours. It would seem to take four months for each mutation. But bacteria divide exponentially so the actual rate of mutation in a growing culture is much faster. Each cell produces two daughter cells so that after two generations there are four cells and after three generations there are eight cells. It takes only eleven generations to get 2048 cells (211 = 2048). At that point you have 2048 c

Geography of the Cell I: Size and Geometry Cells Size and Geometry Introduction How big are viruses? How big is an E. coli cell and what is its mass? How big is http://book.bionumbers.org/what-is-the-mutation-rate-during-genome-replication/ a budding yeast cell? How big is a human cell? How big is https://en.wikipedia.org/wiki/DNA_replication a photoreceptor? What is the range of cell sizes and shapes? Organelles How big are nuclei? How big is the endoplasmic reticulum of cells? How big are mitochondria? How big are chloroplasts? How big is a synapse? Cellular Building Blocks How big are biochemical nuts and bolts? Which is bigger, mRNA or bacterial replication the protein it codes for? How big is the “average” protein? How big are the molecular machines of the central dogma? What is the thickness of the cell membrane? How big are the cell’s filaments? II: Concentrations and Absolute Numbers Making a cell Concentrations and Absolute Numbers - Introduction What is the elemental composition of a cell? What is the density of cells? What are bacterial replication error environmental O2 and CO2 concentrations? What quantities of nutrients need to be supplied in growth media? What is the concentration of bacterial cells in a saturated culture? Cell census What is the pH of a cell? What are the concentrations of different ions in cells? What are the concentrations of free metabolites in cells? What lipids are most abundant in membranes? How many proteins are in a cell? What are the most abundant proteins in a cell? How much cell-to-cell variability exists in protein expression? What are the concentrations of cytoskeletal molecules? How many mRNAs are in a cell? What is the protein to mRNA ratio? What is the macromolecular composition of the cell? Machines and signals What are the copy numbers of transcription factors? What are the absolute numbers of signaling proteins? How many rhodopsin molecules are in a rod cell? How many ribosomes are in a cell? III: Energies and Forces Biology meets physics Energies and Forces - Introduction What is the thermal energy scale and how is it relevant to biology? What is the energy of a hydrogen bond? What is the energy scale associated with the hydrophobic effect? How much

(green). In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. This process occurs in all living organisms and is the basis for biological inheritance. DNA is made up of a double helix of two complementary strands. During replication, these strands are separated. Each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process referred to as semiconservative replication. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication.[1][2] In a cell, DNA replication begins at specific locations, or origins of replication, in the genome.[3] Unwinding of DNA at the origin and synthesis of new strands results in replication forks growing bi-directionally from the origin. A number of proteins are associated with the replication fork to help in the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new strands by adding nucleotides that complement each (template) strand. DNA replication occurs during the S-stage of interphase. DNA replication can also be performed in vitro (artificially, outside a cell). DNA polymerases isolated from cells and artificial DNA primers can be used to initiate DNA synthesis at known sequences in a template DNA molecule. The polymerase chain reaction (PCR), a common laboratory technique, cyclically applies such artificial synthesis to amplify a specific target DNA fragment from a pool of DNA. Contents 1 DNA structures 2 DNA polymerase 3 Replication process 3.1 Initiation 3.2 Elongation 3.3 Replication fork 3.3.1 Leading strand 3.3.2 Lagging strand 3.3.3 Dynamics at the replication fork 3.4 DNA replication proteins 3.5 Replication machinery 3.6 Termination 4 Regulation 4.1 Eukaryotes 4.1.1 Replication focus 4.2 Bacteria 5 Polymerase chain reaction 6 Notes 7 References DNA structures[edit] DNA usu