Editing DNA replication (section)

==== Dynamics at the replication fork ====
[[File:1axc tricolor.png|thumb|200px|The assembled human DNA clamp, a [[trimer (biochemistry)|trimer]] of the protein [[PCNA]]]]

In all cases the helicase is composed of six polypeptides that wrap around only one strand of the DNA being replicated. The two polymerases are bound to the helicase hexamer. In eukaryotes the helicase wraps around the leading strand, and in prokaryotes it wraps around the lagging strand.<ref name="replisome-in-Science">{{Cite journal |display-authors=6 |vauthors=Gao Y, Cui Y, Fox T, Lin S, Wang H, de Val N, Zhou ZH, Yang W |date=February 2019 |title=Structures and operating principles of the replisome |journal=Science |volume=363 |issue=6429 |page=835 |doi=10.1126/science.aav7003 |pmc=6681829 |pmid=30679383}}</ref>

As helicase unwinds DNA at the replication fork, the DNA ahead is forced to rotate. This process results in a build-up of twists in the DNA ahead.<ref>{{Cite book |title=Molecular Biology of the Cell |vauthors=Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |publisher=Garland Science |year=2002 |isbn=0-8153-3218-1 |chapter=DNA Replication Mechanisms: DNA Topoisomerases Prevent DNA Tangling During Replication |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.754#787}}</ref> This build-up creates a torsional load that would eventually stop the replication fork. Topoisomerases are enzymes that temporarily break the strands of DNA, relieving the tension caused by unwinding the two strands of the DNA helix; topoisomerases (including [[DNA gyrase]]) achieve this by adding negative [[DNA supercoil|supercoils]] to the DNA helix.<ref>{{Cite journal |vauthors=Reece RJ, Maxwell A |date=26 September 2008 |title=DNA gyrase: structure and function |journal=Critical Reviews in Biochemistry and Molecular Biology |volume=26 |issue=3–4 |pages=335–375 |doi=10.3109/10409239109114072 |pmid=1657531}}<!--|access-date=7 April 2016--></ref>

Bare single-stranded DNA tends to fold back on itself forming [[Biomolecular structure#Secondary structure|secondary structures]]; these structures can interfere with the movement of DNA polymerase. To prevent this, [[single-strand binding protein]]s bind to the DNA until a second strand is synthesized, preventing secondary structure formation.<ref>{{Cite book |title=Molecular Biology of the Cell |vauthors=Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |publisher=Garland Science |year=2002 |isbn=0-8153-3218-1 |chapter=DNA Replication Mechanisms: Special Proteins Help to Open Up the DNA Double Helix in Front of the Replication Fork |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.754#774}}</ref>

Double-stranded DNA is coiled around [[histone]]s that  play an important role in regulating gene expression so the replicated DNA must be coiled around histones at the same places as the original DNA.<ref>{{Cite journal |last=Koonin |first=Eugene V. |last2=Krupovic |first2=Mart |last3=Ishino |first3=Sonoko |last4=Ishino |first4=Yoshizumi |date=2020-06-09 |title=The replication machinery of LUCA: common origin of DNA replication and transcription |journal=BMC Biology |volume=18 |issue=1 |page=61 |doi=10.1186/s12915-020-00800-9 |issn=1741-7007 |pmc=7281927 |pmid=32517760 |doi-access=free}}</ref> To ensure this, histone [[Chaperone (protein)|chaperones]] disassemble the [[chromatin]] before it is replicated and replace the histones in the correct place. Some steps in this reassembly are somewhat speculative.<ref>{{Cite journal |vauthors=Ransom M, Dennehey BK, Tyler JK |date=January 2010 |title=Chaperoning histones during DNA replication and repair |journal=Cell |volume=140 |issue=2 |pages=183–195 |doi=10.1016/j.cell.2010.01.004 |pmc=3433953 |pmid=20141833}}<!--|access-date=24 July 2020--></ref>

Clamp proteins act as a sliding clamp on DNA, allowing the DNA polymerase to bind to its template and aid in processivity. The inner face of the clamp enables DNA to be threaded through it. Once the polymerase reaches the end of the template or detects double-stranded DNA, the sliding clamp undergoes a conformational change that releases the DNA polymerase. Clamp-loading proteins are used to initially load the clamp, recognizing the junction between template and RNA primers.<ref name="Alberts" /><sup>:274-5</sup>