How long does DNA replication take?
Copying times for human, yeast and bacterial genomes, and why they differ
Matic Broz, PhD7 min
A human cell takes about 8 hours to copy its DNA. That is the length of S phase, the part of the cell cycle in which roughly 6.3 billion base pairs of nuclear DNA are duplicated before the cell divides. Bacteria work on a shorter clock: E. coli copies its 4.6-million-base-pair chromosome in about 40 minutes, and budding yeast copies its genome in 30 to 40 minutes.
The human figure is surprising once you know how slowly the copying machinery moves. A single human replication fork advances only about 25 base pairs per second. The cell finishes in hours only because tens of thousands of starting points along its chromosomes work in parallel, while bacteria solve the same problem with much faster forks and overlapping rounds of copying.
How long does DNA replication take in humans?
In a typical dividing human cell, DNA replication takes about 8 hours. Cooper's textbook describes a rapidly proliferating human cell in culture with a 24-hour cycle: about 11 hours in G1, 8 hours in S phase, 4 hours in G2 and 1 hour in mitosis.[1] Alberts and colleagues give the same 8 hours for S phase in a typical mammalian cell.[2]
That is a typical value, not a constant. Cell Biology by the Numbers puts S phase in many human cell types on the order of 10 hours, and its length shifts with cell type, developmental stage and replication stress.[3] What gets copied is the full diploid set: two copies of the genome spread over 46 chromosomes, about 6.27 billion base pairs in a male cell and 6.37 billion in a female cell, or roughly 2 meters of DNA.[4]
The chromosomes are not copied all at once. Each region has a characteristic time within S phase: open, gene-rich regions tend to replicate early and compact regions later, and the schedule differs between cell types even though the human genome size is the same.[5] The 8 hours is therefore the time until the last region finishes, not the time any one stretch of DNA spends being copied.
Replication is also easy to confuse with sequencing. A cell copies its own chromosomes before it divides, whereas a sequencer reads DNA extracted from a sample, and genome sequencing time depends on entirely different machinery.
How fast does DNA replicate?
An individual human replication fork, the moving point where the double helix is unwound and both strands are copied, advances at roughly 1.5 kilobases per minute, or about 25 base pairs per second.[6] Textbooks often quote a round 50 nucleotides per second for mammalian forks, a value estimated from how fast labeled tracks of new DNA grew in older autoradiography experiments.[2]
In a single-molecule study by Conti and colleagues, forks in primary human keratinocytes averaged 1.46 kb/min (24.3 bp/s), and forks in a keratinocyte-derived cancer cell line averaged 1.67 kb/min (27.8 bp/s). Individual forks varied widely around those means.[6] Budding yeast forks move at almost the same speed, 1.6 kb/min, while E. coli forks are more than 20 times faster.[7][3]
Fork speed is not the same as DNA polymerase speed. A fork is a moving complex of helicase, polymerases, sliding clamps, primase and other proteins, and DNA damage, a short supply of nucleotides or dense chromatin can slow or stall the whole assembly. Fork speed therefore has to be measured in living cells; it cannot be read off the genome sequence.
How do human cells copy their DNA in only 8 hours?
Human cells finish in hours because they start replication at 30,000 to 50,000 origins in each S phase, and every origin launches two forks that move away from each other.[8] Without that parallelism, the slow speed of a single fork would make the job impossible within one cell cycle.
At the primary-cell mean of 1.46 kb/min, we calculate that two forks starting from a single origin would need about 4.1 years to copy 6.3 billion base pairs, treating the diploid DNA as one continuous molecule:
Even one chromosome would be out of reach. Alberts and colleagues calculate that a single fork moving at 50 nucleotides per second would need about 800 hours to copy an average human chromosome of 150 million base pairs.[2]
Cooper's textbook gives the classic picture of how the work is divided: origins spaced about 50 to 300 kb apart, or about 30,000 across the human genome.[9] The origin set has since turned out to be flexible. Cells license many more potential origins than they use, and only 10 to 20% fire in a given mammalian S phase; the unused ones stay in reserve and can fire if nearby forks stall.[10]
Origins also fire in clusters at different times rather than all at once, so each stretch of DNA is copied during only a small part of S phase.[2] How the origins are deployed matters more than any fixed property of the polymerase. Early Drosophila embryos replicate their roughly 120-million-base-pair genome about once every 8 minutes, using an estimated 10,000 origins.[3]
How long does DNA replication take in bacteria?
E. coli copies its chromosome in about 40 minutes under standard laboratory conditions. The circular 4.6-million-base-pair chromosome has a single origin, and the two forks that leave it travel in opposite directions at roughly 500 to 1,000 nucleotides per second until they meet on the far side.[2][10]
The 40-minute figure is the C period, the interval from the start to the end of chromosome replication. Helmstetter and Cooper found it roughly constant at about 40 minutes in cells with doubling times between 20 and 100 minutes, followed by a D period of about 20 minutes before division.[11]
Live-cell measurements with fluorescently tagged replication proteins later reported an average fork speed of about 600 bp/s and replication times of 55 to 65 minutes.[3] Both figures fit their fork speeds: two forks at 1,000 bp/s would copy 4.6 million base pairs in about 38 minutes, and at 600 bp/s in about 64 minutes. The exact value depends on strain, growth conditions and measurement method.
E. coli can divide about every 20 minutes in rich medium, faster than it can copy one chromosome.[3] It manages this by starting new rounds of replication before earlier rounds finish, so a fast-growing cell can hold more than six origins and over ten forks at once, and replication for the next generation is already under way when the cell divides.[3][11]
How does replication time compare across organisms?
Replication time depends on how much DNA there is to copy and how many forks work on it at once, not on genome size alone. The comparison below sets the three best-studied cases side by side.
| Organism | DNA copied | Fork speed | Active origins | Replication time |
|---|---|---|---|---|
| Human (dividing cell) | 6.3 billion bp (diploid) | About 25 bp/s (1.5 kb/min) | 30,000 to 50,000 | About 8 hours (S phase) |
| Budding yeast (S. cerevisiae) | 12.1 million bp (haploid) | About 27 bp/s (1.6 kb/min) | About 300 | 30 to 40 minutes (S phase) |
| E. coli | 4.6 million bp | About 600 to 1,000 bp/s | 1 | About 40 minutes (55 to 65 in live-cell imaging) |
The rows show two strategies. Bacteria rely on speed: one origin, two very fast forks, and overlapping rounds when the cell needs to divide faster than it can copy. Yeast and human cells move their forks about 20 times more slowly but start them at hundreds or tens of thousands of origins. The 8 hours of human S phase measures how many places a cell can start copying, and when, far more than how fast DNA polymerase works.
