AP Syllabus focus:
‘On the leading strand, DNA polymerase synthesizes continuously, whereas on the lagging strand it produces discontinuous fragments that later join.’
DNA replication copies both strands of a double helix at once, but the chemistry of DNA synthesis creates an asymmetry. Understanding how leading and lagging strands are made explains why replication is continuous on one side and fragmented on the other.
Core idea: 5′ to 3′ synthesis forces two different strategies
DNA polymerases can extend a new strand only by adding nucleotides to a free 3′ OH, so new DNA is synthesized 5′ → 3′. Because the two parental strands run antiparallel, the two new strands cannot both be made continuously in the same physical direction at a replication fork.
This diagram maps the replication fork and highlights how antiparallel template orientation forces different synthesis patterns on the two daughter strands. The leading strand is shown being extended continuously toward the fork, while the lagging strand is synthesized discontinuously as Okazaki fragments that are later sealed into a continuous strand by ligase. Labels for helicase, primase, and polymerases connect the strand-level outcome to the enzyme-level mechanism. Source
Replication fork geometry
As the helix opens, each parental strand serves as a template.
Replication fork: The Y-shaped region where parental DNA strands separate and new DNA strands are synthesized.
The two templates at a fork are oriented oppositely, so one template is read toward the fork opening, while the other is read away from it.
Leading strand synthesis (continuous)
What makes it “leading”
The leading strand is synthesized on the template that is oriented so the polymerase can move in the same overall direction as fork progression.
Key features
Continuous synthesis: once started, DNA polymerase can keep adding nucleotides as the fork opens.
Only one start is needed per fork because synthesis can proceed without interruption along the newly exposed template.
The new leading strand’s growing 3′ end stays near the moving fork.
Lagging strand synthesis (discontinuous)
Why it must be fragmented
On the other template strand, polymerase still must synthesize 5′ → 3′, but that direction is opposite the overall movement of the replication fork. The cell solves this by repeatedly starting new short stretches of DNA as more template becomes exposed.
Okazaki fragment: A short segment of newly synthesized DNA made discontinuously on the lagging strand, later joined into a continuous strand.
A lagging strand therefore accumulates multiple fragments behind the fork.
Key features
Discontinuous synthesis: many separate DNA pieces are produced.
Each fragment begins near the fork (on newly exposed template) and extends away from the fork until it reaches the previous fragment.
Over time, fragments later join to form one continuous lagging strand.
Coordinating leading and lagging synthesis at one fork
Even though the products look different (one long strand versus many fragments), both strands are replicated at the same fork and must stay coordinated.
The fork exposes template for both strands simultaneously.
Polymerase activity on the lagging strand occurs in cycles (start a fragment, extend, then start again) so overall replication can keep pace with fork movement.
This figure illustrates one mechanistic solution for coordinating synthesis at a single fork: the lagging-strand template forms a transient loop so the lagging-strand polymerase can synthesize while staying associated with the replisome. As each Okazaki fragment is extended, the loop grows and is then released, explaining the cyclical start–extend–restart pattern. The labeled helicase, primers, and Okazaki fragments connect the looping geometry to discontinuous lagging-strand production. Source
The end result is two daughter DNA molecules in which each contains one original strand paired with one newly synthesized strand, achieved through continuous leading-strand synthesis and discontinuous lagging-strand synthesis.
FAQ
Cells physically couple the enzymes in a single replisome so both strands are synthesised in a coordinated way.
One common model is the lagging-strand template looping out and back so synthesis can proceed while the fork advances, then the loop resets for the next fragment.
Fragment length reflects how often new starts are made on the lagging strand and how quickly extension proceeds before the next fragment is encountered.
It varies by organism and is influenced by replisome organisation and chromatin packaging in eukaryotes.
Because the template for the lagging strand is revealed progressively as the fork opens, a start can only occur on template that is already single-stranded.
As the fork advances, new stretches become available, requiring additional starts to copy them.
When forks converge, the remaining unreplicated region is filled in and any remaining nicks are sealed.
This ensures each daughter strand becomes continuous across the former junction point.
At a linear chromosome end, the final lagging-strand start can leave an unfilled region after the last initiating segment is removed.
Eukaryotes address this end-replication problem using telomere maintenance mechanisms to prevent progressive shortening.
Practice Questions
Describe the difference between leading- and lagging-strand DNA synthesis during replication. (3 marks)
Leading strand is synthesised continuously (1)
Lagging strand is synthesised discontinuously as short fragments (1)
Fragments are later joined to form a continuous strand / named as Okazaki fragments (1)
Explain why DNA replication produces a leading strand and a lagging strand at each replication fork, and describe how the lagging strand is produced. (6 marks)
DNA strands are antiparallel (1)
DNA polymerase can only synthesise new DNA in the direction (1)
Therefore only one new strand can be made continuously in the same direction as fork movement (leading strand) (1)
The other strand must be made in short sections as more template is exposed (1)
These sections are Okazaki fragments (1)
Okazaki fragments are later joined to make a continuous strand (1)
