Editing DNA synthesis (section)

==DNA replication==
[[File:Asymmetry in the synthesis of leading and lagging strands.svg|thumb|left|Overview of the steps in DNA replication]]
[[File:DNA replication en.svg|upright=1.25|thumb|right|DNA replication, and the various enzymes involved]]

In nature, DNA molecules are synthesised by all living [[Cell (biology)|cells]] through the process of [[DNA replication]]. This typically occurs as a part of [[cell division]]. [[DNA replication]] occurs so, during cell division, each daughter cell contains an accurate copy of the genetic material of the cell. ''In vivo'' DNA synthesis ([[DNA replication]]) is dependent on a complex set of [[enzymes]] which have evolved to act during the [[S phase]] of the cell cycle, in a concerted fashion. In both [[eukaryotes]] and [[prokaryotes]], [[DNA replication]] occurs when specific [[topoisomerases]], [[helicases]] and [[gyrases]] (replication initiator proteins) [[Helicase|uncoil]] the double-stranded DNA, exposing the nitrogenous bases.<ref name="Pelt-Verkuil">{{cite book |last1=Pelt-Verkuil |first1=Evan |chapter=A Brief Comparison Between in Vivo DNA Replication and in Vitro PCR Amplification |title=Principles and Technical Aspects of PCR Amplification |date=2008 |publisher=Springer Netherlands |location=Rotterdam |pages=9–15 |doi=10.1007/978-1-4020-6241-4_2 |isbn=978-1-4020-6240-7 |s2cid=215257488 |url=https://link.springer.com/content/pdf/10.1007%2F978-1-4020-6241-4_2.pdf}}</ref> These enzymes, along with accessory proteins, form a macromolecular machine which ensures accurate duplication of DNA sequences. Complementary base pairing takes place, forming a new double-stranded DNA molecule. This is known as '''semi-conservative''' replication since one strand of the new DNA molecule is from the 'parent' strand.

Continuously, eukaryotic enzymes encounter DNA damage which can perturb DNA replication. This damage is in the form of DNA lesions that arise spontaneously or due to DNA damaging agents. DNA replication machinery is therefore highly controlled in order to prevent collapse when encountering damage.<ref>{{cite journal |last1=Patel |first1=Darshil R. |last2=Weiss |first2=Robert S. |title=A tough row to hoe: when replication forks encounter DNA damage |journal=Biochem Soc Trans |date=2018 |volume=46 |issue=6 |pages=1643–1651 |doi=10.1042/BST20180308 |pmid=30514768|pmc=6487187 }}</ref> Control of the DNA replication system ensures that the genome is replicated only once per cycle; over-replication induces DNA damage. Deregulation of DNA replication is a key factor in genomic instability during cancer development.<ref>{{cite journal |last1=Reusswig |first1=Karl-Uwe |last2=Pfander |first2=Boris |title=Control of Eukaryotic DNA replication Initiation - Mechanisms to Ensure Smooth Transitions |journal=Genes (Basel) |date=2019 |volume=10 |issue=2 |page=99 |doi=10.3390/genes10020099 |pmid=30700044|pmc=6409694 |doi-access=free }}</ref>

This highlights the specificity of DNA synthesis machinery ''in vivo''. Various means exist to artificially stimulate the replication of naturally occurring DNA, or to create artificial gene sequences. However, DNA synthesis ''in vitro'' can be a very error-prone process.

===DNA repair synthesis===

[[DNA damage (naturally occurring)|Damaged DNA]] is subject to repair by several different [[DNA repair|enzymatic repair processes]], where each individual process is specialized to repair particular types of damage.  The DNA of humans is subject to damage from multiple natural sources and insufficient repair is associated with disease and [[DNA damage theory of aging|premature aging]].<ref name = Tiwari2019>Tiwari V, Wilson DM 3rd.  DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging.  Am J Hum Genet. 2019 Aug 1;105(2):237-257. doi: 10.1016/j.ajhg.2019.06.005. Review.  PMID 31374202</ref>   Most DNA repair processes form single-strand gaps in DNA during an intermediate stage of the repair, and these gaps are filled in by repair synthesis.<ref name = Tiwari2019/>  The specific repair processes that require gap filling by DNA synthesis include [[nucleotide excision repair]], [[base excision repair]], [[mismatch repair]], [[homologous recombination]]al repair, [[non-homologous end joining]] and [[microhomology-mediated end joining]].