Editing Endonuclease (section)

== Processes involved with endonucleases ==
Endonucleases play a role in many aspects of biological life. Below are a couple examples of processes where endonucleases play a crucial role.

=== DNA repair ===
Endonucleases play a role in DNA repair. [[AP endonuclease]], specifically, catalyzes the incision of DNA exclusively at AP sites, and therefore prepares DNA for subsequent excision, repair synthesis and DNA ligation. For example, when depurination occurs, this lesion leaves a deoxyribose sugar with a missing base.<ref name="isbn1-55581-319-4">{{cite book |title=DNA repair and mutagenesis |vauthors=Ellenberger T, Friedberg EC, Walker GS, Wolfram S, Wood RJ, Schultz R |publisher=ASM Press |year=2006 |isbn=978-1-55581-319-2 |location=Washington, D.C.}}</ref> The AP endonuclease recognizes this sugar and essentially cuts the DNA at this site and then allows for DNA repair to continue.<ref name="isbn0-8153-3218-1">{{cite book |author=Alberts B |title=Molecular biology of the cell |publisher=Garland Science |year=2002 |isbn=978-0-8153-3218-3 |location=New York}}</ref> ''E. coli'' cells contain two AP endonucleases: endonuclease IV (endoIV) and exonuclease III (exoIII) while in eukaryotes, there is only one AP endonuclease.<ref name="pmid12483517">{{cite journal |vauthors=Nishino T, Morikawa K |date=December 2002 |title=Structure and function of nucleases in DNA repair: shape, grip and blade of the DNA scissors |journal=Oncogene |volume=21 |issue=58 |pages=9022–32 |doi=10.1038/sj.onc.1206135 |pmid=12483517 |doi-access=free}}</ref>

[[File:APEndonucleasecartoon.gif|APEndonucleasecartoon]]

==== DNA crosslink repair ====
[[DNA repair|Repair of DNA]] in which the two complementary strands are joined by an [[crosslinking of DNA|interstrand covalent crosslink]] requires multiple incisions in order to disengage the strands and remove the damage.  Incisions are required on both sides of the crosslink and on both strands of the duplex DNA.  In mouse embryonic stem cells, an intermediate stage of crosslink repair involves production of double-strand breaks.<ref name="Hanada2006">{{cite journal |last1=Hanada |first1=K. |last2=Budzowska |first2=M. |last3=Modesti |first3=M. |last4=Maas |first4=A. |last5=Wyman |first5=C. |last6=Essers |first6=J. |last7=Kanaar |first7=R. |date=2006 |title=The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks |journal=The EMBO Journal |volume=25 |issue=20 |pages=4921–4932 |doi=10.1038/sj.emboj.7601344 |pmc=1618088 |pmid=17036055}}</ref>   [[MUS81]]/[[EME1]] is a structure specific endonuclease involved in converting interstrand crosslinks to double-strand breaks in a DNA replication-dependent manner.<ref name="Hanada2006" />  After introduction of a double-strand break, further steps are required to complete the repair process.  If a crosslink is not properly repaired it can block [[DNA replication]].{{citation needed|date=January 2023}}

==== Thymine dimer repair ====
Exposure of [[Escherichia virus T4|bacteriophage (phage) T4]] to [[ultraviolet]] irradiation induces [[pyrimidine dimer|thymine dimers]] in the phage DNA.  The phage T4 ''denV'' gene encodes [[endonuclease V]] that catalyzes the initial steps in the repair of these UV-induced thymine dimers.<ref>{{Cite journal |last1=Bernstein |first1=C. |date=1981 |title=Deoxyribonucleic acid repair in bacteriophage |journal=Microbiological Reviews |volume=45 |issue=1 |pages=72–98 |doi=10.1128/mr.45.1.72-98.1981 |pmc=281499 |pmid=6261109}}</ref>  Endonuclease V first cleaves the glycosylic bond on the 5’ side of a pyrimidine dimer and then catalyzes cleavage of the DNA phosphodiester bond that originally linked the two nucleotides of the dimer. Subsequent steps in the repair process involve removal of the dimer remnants and repair synthesis to fill in the resulting single-strand gap using the undamaged strand as template.{{citation needed|date=January 2023}}

=== Apoptosis ===
During apoptosis, Apoptotic endonuclease [[Caspase-activated DNase|DFF40]] is activated to initiate controlled cellular disassembly. This  disintegration is characterized by the cleavage of genomic DNA into specific fragments. The precise role of endonucleases in this context is to cleave the DNA at specific sites, generating fragments with defined lengths. These fragments are then packaged into apoptotic bodies, ensuring a neat and efficient removal of the dying cell without causing inflammation or damage to neighboring cells.<ref>{{Cite journal |last1=Yoshida |first1=Akira |last2=Pommier |first2=Yves |last3=Ueda |first3=Takanori |date=2006-02-01 |title=Endonuclease Activation and Chromosomal DNA Fragmentation during Apoptosis in Leukemia Cells |url=https://doi.org/10.1007/BF03342699 |journal=International Journal of Hematology |language=en |volume=84 |issue=1 |pages=31–37 |doi=10.1007/BF03342699 |pmid=16867899 |s2cid=25475000 |issn=1865-3774|url-access=subscription }}</ref>

=== DNA Replication ===
[[Flap structure-specific endonuclease 1|Flap endonuclease 1 (FEN1)]] and Dna2 endonuclease are integral to [[DNA replication]] on the lagging strand, participating in crucial processes such as primer removal and [[Okazaki fragments|Okazaki]] fragment processing. Endonucleases are actively involved in processing these fragments by cleaving the phosphodiester bonds between them. This process is integral to the seamless synthesis and joining of Okazaki fragments, contributing to the overall continuity of the newly replicated DNA strand.<ref>{{Cite journal |last1=Jin |first1=Yong Hwan |last2=Obert |first2=Robyn |last3=Burgers |first3=Peter M. J. |last4=Kunkel |first4=Thomas A. |last5=Resnick |first5=Michael A. |last6=Gordenin |first6=Dmitry A. |date=2001-04-24 |title=The 3′→5′ exonuclease of DNA polymerase δ can substitute for the 5′ flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=98 |issue=9 |pages=5122–5127 |doi=10.1073/pnas.091095198 |doi-access=free |issn=0027-8424 |pmid=11309502|pmc=33174 }}</ref><ref>{{Cite journal |last1=Liu |first1=Yuan |last2=Kao |first2=Hui-I |last3=Bambara |first3=Robert A. |date=June 2004 |title=Flap Endonuclease 1: A Central Component of DNA Metabolism |url=https://www.annualreviews.org/doi/10.1146/annurev.biochem.73.012803.092453 |journal=Annual Review of Biochemistry |language=en |volume=73 |issue=1 |pages=589–615 |doi=10.1146/annurev.biochem.73.012803.092453 |pmid=15189154 |issn=0066-4154|url-access=subscription }}</ref>

=== RNA Processing ===
Endonucleases, more specifically [[endoribonuclease]], play a crucial role in RNA processing, a fundamental step in gene expression. This process involves the precise cleavage of precursor RNA molecules, guided by endonucleases, to generate functional RNAs essential for various cellular functions. Endonucleases selectively cleave precursor RNAs at specific sites, defining the boundaries of functional RNA segments during RNA processing. The outcome of RNA processing is the production of functional RNA molecules, such as [[Transfer RNA|transfer RNAs (tRNAs)]] and [[Ribosomal RNA|ribosomal RNAs (rRNAs)]]. Endonucleases contribute to the precision of this process, ensuring the formation of mature and functional RNA species.

Endonucleases like [[Ribonuclease P|RNase P]] and [[Ribonuclease Z|tRNase Z]] (ELAC2), shape precursor tRNAs into mature, functional tRNAs, crucial for accurate translation during protein synthesis.<ref>{{Cite journal |last1=Hartmann |first1=Roland K. |last2=Gössringer |first2=Markus |last3=Späth |first3=Bettina |last4=Fischer |first4=Susan |last5=Marchfelder |first5=Anita |date=2009 |title=The making of tRNAs and more - RNase P and tRNase Z |url=https://pubmed.ncbi.nlm.nih.gov/19215776/ |journal=Progress in Molecular Biology and Translational Science |volume=85 |pages=319–368 |doi=10.1016/S0079-6603(08)00808-8 |issn=1877-1173 |pmid=19215776}}</ref> In ribosome biogenesis, endonucleases from the [[Ribonuclease III|RNase III family]], like [[Drosha|DROSHA]], play a role in processing precursor rRNAs, contributing to the assembly of functional ribosomes.<ref>{{Cite journal |last1=Lejars |first1=Maxence |last2=Kobayashi |first2=Asaki |last3=Hajnsdorf |first3=Eliane |date=December 2021 |title=RNase III, Ribosome Biogenesis and Beyond |journal=Microorganisms |language=en |volume=9 |issue=12 |page=2608 |doi=10.3390/microorganisms9122608 |doi-access=free |pmid=34946208|pmc=8708148 }}</ref>

[[Dicer|DICER]] and [[Drosha|DROSHA]] also from the RNase III family play a role in the processing pre-miRNA to functional miRNA.<ref>{{Cite journal |last1=Kuehbacher |first1=Angelika |last2=Urbich |first2=Carmen |last3=Zeiher |first3=Andreas M. |last4=Dimmeler |first4=Stefanie |date=2007-07-06 |title=Role of Dicer and Drosha for Endothelial MicroRNA Expression and Angiogenesis |url=https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.107.153916 |journal=Circulation Research |language=en |volume=101 |issue=1 |pages=59–68 |doi=10.1161/CIRCRESAHA.107.153916 |pmid=17540974 |issn=0009-7330}}</ref>

=== Maturation of Nails and Hairs ===
The endonuclease [[DNASE1L2|DNase1L2]] also contribute prominently to the removal of DNA during the formation of hair and nails. This process is essential for the [[Cellular differentiation|maturation]] of hair and nail structures and is crucial for the transformation of cells into durable and [[keratin]]ized structures, ensuring the strength and integrity of hair and nails.<ref>{{Cite journal |last1=Fischer |first1=Heinz |last2=Szabo |first2=Sandra |last3=Scherz |first3=Jennifer |last4=Jaeger |first4=Karin |last5=Rossiter |first5=Heidemarie |last6=Buchberger |first6=Maria |last7=Ghannadan |first7=Minoo |last8=Hermann |first8=Marcela |last9=Theussl |first9=Hans-Christian |last10=Tobin |first10=Desmond J. |last11=Wagner |first11=Erwin F. |last12=Tschachler |first12=Erwin |last13=Eckhart |first13=Leopold |date=June 2011 |title=Essential role of the keratinocyte-specific endonuclease DNase1L2 in the removal of nuclear DNA from hair and nails |journal=The Journal of Investigative Dermatology |volume=131 |issue=6 |pages=1208–1215 |doi=10.1038/jid.2011.13 |issn=0022-202X |pmc=3185332 |pmid=21307874}}</ref>