Editing Embryonic stem cell (section)

===Repair of DNA damage===
Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage.  For instance, human foreskin fibroblasts, one type of somatic cell, use [[Non-homologous end joining|non-homologous end joining (NHEJ)]], an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.<ref name="pmid18769152">{{cite journal |vauthors=Mao Z, Bozzella M, Seluanov A, Gorbunova V |title=DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells |journal=Cell Cycle |volume=7 |issue=18 |pages=2902–2906 |date=September 2008 |pmid=18769152 |pmc=2754209 |doi=10.4161/cc.7.18.6679}}</ref>   Because of its error-prone nature, NHEJ tends to produce mutations in a cell's clonal descendants.

ES cells use a different strategy to deal with DSBs.<ref name=Tichy>{{cite journal |vauthors=Tichy ED, Pillai R, Deng L |title=Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks |journal=Stem Cells Dev. |volume=19 |issue=11 |pages=1699–1711 |date=November 2010 |pmid=20446816 |pmc=3128311 |doi=10.1089/scd.2010.0058 |display-authors=etal}}</ref>  Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently, robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages.  Thus, mouse ES cells predominantly use high fidelity [[Homology directed repair|homologous recombinational repair (HRR)]] to repair DSBs.<ref name=Tichy />  This type of repair depends on the interaction of the two sister chromosomes{{Verify source|date=June 2020}} formed during S phase and present together during the G2 phase of the cell cycle.  HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome.  Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes aren't present).  Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage.<ref>{{cite journal |vauthors=Hong Y, Stambrook PJ |title=Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue=40 |pages=14443–14448 |date=October 2004 |pmid=15452351 |pmc=521944 |doi=10.1073/pnas.0401346101 |bibcode=2004PNAS..10114443H |doi-access=free }}</ref>  Rather they undergo programmed cell death (apoptosis) in response to DNA damage.<ref name="pmid9443911">{{cite journal |vauthors=Aladjem MI, Spike BT, Rodewald LW |title=ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage |journal=Curr. Biol. |volume=8 |issue=3 |pages=145–155 |date=January 1998 |pmid=9443911 |doi=10.1016/S0960-9822(98)70061-2|s2cid=13938854 |display-authors=etal|doi-access=free }}</ref>  Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer.<ref name="pmid12052432">{{cite journal |vauthors=Bernstein C, Bernstein H, Payne CM, Garewal H |title=DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis |journal=Mutat. Res. |volume=511 |issue=2 |pages=145–178 |date=June 2002 |pmid=12052432 |doi=10.1016/S1383-5742(02)00009-1}}</ref>   Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells.<ref>{{cite journal |vauthors=Cervantes RB, Stringer JR, Shao C, Tischfield JA, Stambrook PJ |title=Embryonic stem cells and somatic cells differ in mutation frequency and type |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue=6 |pages=3586–3590 |date=March 2002 |pmid=11891338 |pmc=122567 |doi=10.1073/pnas.062527199 |bibcode=2002PNAS...99.3586C |doi-access=free }}</ref>