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Pathway Description
DNA Replication Fork
Homo sapiens
Metabolic Pathway
Created: 2013-08-22
Last Updated: 2019-08-13
DNA is composed of two long and complementary strands, with a backbone on the outside and nucleotides in the middle. During replication the two strands of DNA separate; the resulting structure is called the replication fork. The replication fork forms because enzymes called helicases surround the DNA strands and break the hydrogen bonds which hold them together. The result is that two long branches, almost like fork prongs, each of which is a DNA strand.
Replication of DNA has two main different processes. Because DNA is replicated in the 5' to 3' direction, and because both DNA strands in the replication fork are negative mirror images of each other, and because the replication fork is created on only one direction down the length of the DNA, two types of replication strands are formed: the leading and the lagging strand.
These strands are so named by the way in which DNA polymerase reads the original DNA strand and attaches the complementary nucleotides as it makes its way along the chain. Because the direction of the movement of the replication fork, and the direction of the addition of nucleotides in the leading strand is the same, the process is continuous.That is, a polymerase is able to read the DNA and add the matching nucleotide bases to it continuously. In prokaryotes DNA polymerase III is responsible for creating the leading strand.
The lagging strand is oriented in the opposite direction to the leading strand. Thus, replication of the lagging strand occurs in the opposing direction to that of the leading strand and the replication fork. As a result, replication of the lagging strand is a slower and more complicated process than that of the leading strand. Thus it is seen to lag behind the leading strand (hence the name).
References
DNA Replication Fork References
McCulloch SD, Kunkel TA: The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res. 2008 Jan;18(1):148-61. doi: 10.1038/cr.2008.4.
Pubmed: 18166979
Rossi, M. (2011). Distinguishing the pathways of primer removal during Eukaryotic Okazaki fragment maturation (Ph.D). University of Rochester. http://hdl.handle.net/1802/6537
Zheng L, Zhou M, Guo Z, Lu H, Qian L, Dai H, Qiu J, Yakubovskaya E, Bogenhagen DF, Demple B, Shen B: Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates. Mol Cell. 2008 Nov 7;32(3):325-36. doi: 10.1016/j.molcel.2008.09.024.
Pubmed: 18995831
Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC: BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011 Feb 15;25(4):350-62. doi: 10.1101/gad.2003811.
Pubmed: 21325134
Ronchi D, Di Fonzo A, Lin W, Bordoni A, Liu C, Fassone E, Pagliarani S, Rizzuti M, Zheng L, Filosto M, Ferro MT, Ranieri M, Magri F, Peverelli L, Li H, Yuan YC, Corti S, Sciacco M, Moggio M, Bresolin N, Shen B, Comi GP: Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability. Am J Hum Genet. 2013 Feb 7;92(2):293-300. doi: 10.1016/j.ajhg.2012.12.014. Epub 2013 Jan 24.
Pubmed: 23352259
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