SCR7 |
Catalog No.GC12106 |
SCR7 est une forme instable qui peut être autocyclisée en une forme stable SCR7 pyrazine. La SCR7 pyrazine est un inhibiteur de l'ADN ligase IV qui bloque la liaison terminale non homologue (NHEJ) d'une manière dépendante de la ligase IV. La pyrazine SCR7 est également un activateur CRISPR/Cas9 qui augmente l'efficacité de la réparation dirigée par l'homologie (HDR) médiée par Cas9. La pyrazine SCR7 induit l'apoptose cellulaire et a une activité anticancéreuse.
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Cas No.: 1533426-72-0
Sample solution is provided at 25 µL, 10mM.
Scr7 is a DNA ligase IV inhibitor, initially identified as an anti-cancer agent [1].
Scr7 targets the DNA binding domain of DNA ligase IV, reducing its affinity for double strand breaks (DSBs) and inhibiting its function. Scr7 also inhibits DNA ligase III (but not DNA ligase I), albeit less efficiently. Cells were treated with doxycycline to induce Cas9 expression, with various concentrations of Scr7 for 24 h. Scr7 maintained cells capable of entering S/G2 phase, which is necessary for HDR. [1] Treatment of mice with Scr7 affects lymphocyte development, as DNA ligase IV plays a key role in the joining of coding ends during V(D)J recombination by means of C-NHEJ16. The defects in lymphocyte development upon Scr7 treatment are transient and reversible, due to the noncovalent mode of binding of Scr7. Scr7 enhanced the frequency of HDR by transiently blocking NHEJ (with the exception of DNA ligase I–dependent alt-NHEJ), resulting in precise genome editing by CRISPR-Cas9 in both cultured cells and in mice. [2]
References:
[1]. Srivastava M, Nambiar M, Sharma S et al. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012 Dec 21;151(7):1474-87. doi: 10.1016/j.cell.2012.11.054.
[2]. Maruyama T, Dougan SK, Truttmann MC et al.Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol. 2015 Mar 23. doi: 10.1038/nbt.3190. [Epub ahead of print]
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