Fork Regression
Fork Regression - Related Videos
02:37
Restarting Stalled Replication Forks
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2020
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
01:02
The DNA Replication Fork
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2020
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
01:02
The DNA Replication Fork
0 Views •
2023
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
01:52
Regression Toward the Mean
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2020
Regression toward the mean (“RTM”) is a phenomenon in which extremely high or low values—for example, and individual’s blood pressure at a particular moment—appear closer to a group’s average upon remeasuring. Although this statistical peculiarity is the result of random error and chance, it has been problematic across various medical, scientific, financial and psychological applications. In particular, RTM, if not taken into account, can interfere when researchers try to extrapolate results...
07:27
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Cited by 10 •
2010
The fate of the replisome following a collision with a head-on RNA polymerase (RNAP) is unknown. We find that the replisome stalls upon collision with a head-on RNAP, but resumes elongation after displacing the RNAP from DNA. Mfd promotes replication restart by facilitating displacement of the RNAP after the collision.
FAQs
Replication forks may stall when they encounter DNA lesions, insufficient nucleotide supplies, or proteins that remain tightly bound to DNA. These obstacles interrupt normal fork progression and create a replication intermediate that can be processed rather than abandoned. Recognizing these triggers helps explain why fork regression forms part of the cellular response to replication stress.
The four-way junction reorganizes the stalled replication fork and helps stabilize exposed DNA while replication cannot proceed normally. This temporary structure gives the cell time to address the obstruction through lesion bypass, repair, or replication restart. Its protective value depends on controlled processing, because an unstable or improperly handled intermediate can threaten chromosome integrity.
Nucleases can process regressed fork structures, but excessive or uncontrolled processing may convert a protective intermediate into a source of chromosome breaks. This creates a critical balance: regression can preserve DNA and support recovery, whereas inappropriate nuclease action can increase damage. That relationship helps connect replication-fork processing with genome instability.
A stalled fork does not necessarily represent permanent replication failure. Regression reorganizes the fork so exposed DNA remains stabilized while the cell gains time for lesion bypass, repair, or restart. By creating an opportunity to resolve the obstacle before replication resumes, the process can support accurate genome duplication, although faulty processing may produce the opposite outcome.
Studies can focus on the conditions that impede fork movement, the formation of the regressed four-way junction, and the consequences of processing that structure. Researchers also consider whether the intermediate supports lesion bypass, repair, or replication restart, or instead leads to chromosome breaks. These questions connect the immediate fork response with broader genome-maintenance mechanisms.
Fork regression provides a framework for understanding how cells protect chromosomes when replication encounters obstacles. If this response or its processing becomes defective, stalled forks may be resolved inaccurately, increasing genome instability. That connection makes the process relevant to cancer biology and to inherited disorders in which DNA repair and genome maintenance are impaired.