Part of the cell · Genome replication, segregation and repair
Copying and repairing the genome
On the cell picture: Dna replication, Dna repair
Copying DNA accurately, separating the two copies, and continuously repairing chemical damage — which at 95 °C is relentless.
Proteins in the model: 56
Part of the model's 1051 proteins. Each group below is a book group, counted in the working count after the repeats and non-first-cell groups were removed. The proteins are not yet matched gene by gene.
| Group | Proteins |
|---|---|
| DNA replication initiation | 7 |
| DNA replication primase | 1 |
| DNA replication core | 7 |
| DNA replication termination | 3 |
| DNA Supercoiling Control | 5 |
| Auxiliary DNA replication | 2 |
| DNA repair | 8 |
| Chromosome segregation | 2 |
| DNA mismatch recognition | 6 |
| DNA Topoisomerase | 1 |
| DNA topology management | 2 |
| DNA precursor synthesis | 4 |
| DNA precursor metabolism | 8 |
Its pathways
- DNA damage repairatlas pathway7
- DNA synthesisatlas pathway5
- Topology managementatlas pathway4
- Joining and end processingatlas pathway3
- Recombination and restartatlas pathway2
- Chromosome preparationatlas pathway1
- Initiation and openingatlas pathway1
- Homologous recombinationKEGG map5
- Base excision repairKEGG map3
- Cysteine and methionine metabolismKEGG map2
- Not yet placed in a pathwayto sort22
If it fails
No usable copy of the genome is produced, or damage accumulates faster than it can be repaired.
Dies at once · within the current generation
What it depends on
- Making DNA and RNA lettersDeoxyribonucleotides are the monomers used to replicate and repair DNA.Book pp. 499–501
- Turning hydrogen into usable energyATP powers selected helicase, ligase, and chromosome-management reactions.Book pp. 501
- Reading genes into RNA, Building proteins and folding themTranslation produces the proteins that carry out DNA replication, repair, and segregation.Book pp. 501–502
What it supplies
- Reading genes into RNA, Building proteins and folding themMaintained DNA provides templates encoding mRNAs, functional RNAs, and the translation machinery.Book pp. 501–502
- Dividing into two cellsChromosome replication and segregation must be coordinated with cellular partitioning.Book pp. 501, 504
Dependencies are curated from the book at the level of the map’s systems and are not measured protein contacts. See all systems together.
How it is built and controlled
Counts from UniProt annotations of this group’s proteins.
Its place in the control layer
Information
- Copying the genome: , , , , , , , , , , ,
From the control-layer pages. Which genes a regulator controls is mostly inferred from related bacteria, because Aquifex has no genetic system for testing it directly.
Origins
What needs to be explained
How did copying, strand separation and error control first become linked?
What needs explaining. Explain template copying, sufficient fidelity and chromosome management, distinguishing plausible early copying from modern DNA replication.
Hurdles
- H-GEN-1Faithful copyingThe problem. A genome of over a million bases must be copied with fewer than about one error per million bases, which cells achieve with proofreading polymerases and repair enzymes.Why it is hard. Copying without enzymes makes errors at rates of several percent per base, too high to keep a sequence of useful length.Information and controlStage 2: One step shown on its ownShown: Short templates have been copied without enzymes, but not over repeated rounds.In the books: 112 open problems on dna processing ↗
- H-GEN-2DNA building blocksThe problem. Cells make DNA building blocks from RNA building blocks with ribonucleotide reductase, a complex radical enzyme.Why it is hard. Prebiotic routes to deoxyribose and deoxynucleotides give low yields, and the enzyme that makes them in cells is itself a large protein.Chemistry before lifeStage 1: Ingredients made under plausible early-Earth conditionsShown: Prebiotic routes to some DNA building blocks have been reported.In the books: 112 open problems on dna processing ↗
- H-GEN-3Copying and separationThe problem. Replication needs a helicase to open the double helix, a primase, a polymerase, a sliding clamp, a ligase and gyrase to relieve twisting.Why it is hard. Separating long double strands by heat also destroys other components; enzymatic separation needs the replication proteins themselves.Molecular machinesStage 2: One step shown on its ownShown: Copying short templates and separating strands by heating have each been shown on their own.In the books: 112 open problems on dna processing ↗
- H-GEN-4Error thresholdThe problem. To keep its information, a genome must be copied with fewer errors than about one per genome length per generation.Why it is hard. Above that error rate the information degrades with every copy. Staying below it needs proofreading and repair proteins, which the genome itself must encode.Information and controlStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 112 open problems on dna processing ↗
- H-GEN-5Replication–division couplingThe problem. Each daughter cell must receive a complete genome, so copying must finish and the copies be separated before division.Why it is hard. Cells coordinate this with dedicated proteins (DnaA, SMC and partitioning proteins); without them daughters can be left without genes.The integrated cellStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 112 open problems on dna processing ↗
Scope. A requirement of modern DNA cells is not automatically a requirement of the earliest hereditary system. Origin hypotheses must specify their proposed starting chemistry.
Experimental progress. Single-molecule experiments show dynamic behavior of bacterial replication polymerases, helping distinguish functional coordination from rigid synchronization.
What would strengthen a natural account. Steps shown to work together under plausible early-Earth conditions, without a chemist choosing the reagents, purifying the products or changing conditions between steps, would strengthen a natural account of origins in proportion to what they explain. Loss of a claimed dependency or discovery of functional alternatives would weaken the corresponding design argument. Gaps in the record do not supply a numerical likelihood for either explanation.
Observations. Template copying coordinates strand separation with repeated nucleotide addition. DNA twisting and entanglement must be managed during replication and chromosome handling.
Hallmarks that apply.
- H18 Processive copying: Template copying coordinates strand separation with repeated nucleotide addition.
- H19 Topological control: DNA twisting and entanglement must be managed during replication and chromosome handling.
- H33 Multi-level error monitoring: Proofreading and repair address different copying errors or lesions; pathways are organism-specific.
The author’s conclusion. The coordinated features give the author a positive reason to consider design within the wider cellular architecture. For this local system alone, they do not establish that design is uniquely the best historical explanation. The conservative inference is that the system contributes to a cumulative design case, with its weight conditional on the comparative evidence and on how much plausible natural pathways explain.
From the book article DNA Processing, with its scientific references.
How it was discovered
- 1953Watson and Crick point out that DNA base pairing suggests how the molecule could be copied.Watson & Crick, Nature 171:964–967 (1953)
- 1956Arthur Kornberg discovers DNA polymerase, the enzyme that builds new DNA on a template (Nobel Prize 1959).Kornberg et al., Biochimica et Biophysica Acta 21:197–198 (1956)
- 1958Meselson and Stahl show that each new DNA molecule keeps one old strand and gains one new one.Meselson & Stahl, PNAS 44:671–682 (1958)
- 1968Okazaki and colleagues find that one DNA strand is copied in short pieces that are later joined.Okazaki et al., PNAS 59:598–605 (1968)
- 1976Gellert and colleagues discover DNA gyrase, which relieves the twisting that copying creates.Gellert et al., PNAS 73:3872–3876 (1976)
- 1993Tomas Lindahl shows that DNA decays on its own in water, so constant repair is needed (Nobel Prize 2015).Lindahl, Nature 362:709–715 (1993)
Each hurdle above is sorted by kind and by how far experiments have got (see “How hurdles are sorted” at the top).
All parts of the cell side by side: origins hub. The book articles:
- DNA Processing: system page · full description · origins