A stapled POL κ peptide targets REV1 to inhibit mutagenic translesion synthesis.

A stapled POL κ peptide targets REV1 to inhibit mutagenic translesion synthesis.
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钉钉的polκ肽靶向Rev1以抑制诱变转移合成。

DOI:
10.1002/em.22395
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发表时间:
2020-10
影响因子:
2.8
通讯作者:
Walker GC
Walker GC
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Chatterjee N;D'Souza S;Shabab M;Harris CA;Hilinski GJ;Verdine GL;Walker GC

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DNA POL κ的钉接α-螺旋RIR (Rev1相互作用区)肽比未钉接肽更有效地结合到翻译合成DNA聚合酶Rev1的c端募集域的RIR界面上。结合最紧密的钉状肽易位到细胞中,增强DNA损伤剂的细胞毒性,同时减少突变。具有这些特征的药物可能作为佐剂,通过抑制rev1依赖性的诱变转译合成来改善化疗和减少获得性耐药。
Stapled α-helical RIR (Rev1-interacting region) peptides of DNA POL κ bind more effectively to the RIR-interface of the C-terminal recruitment domain of the translesion synthesis DNA polymerase Rev1 than unstapled peptide. The tightest-binding stapled peptide translocates into cells and enhances the cytotoxicity of DNA damaging agents while reducing mutagenesis. Drugs with these characteristics could potentially serve as adjuvants to improve chemotherapy and reduce acquired resistance by inhibiting Rev1-dependent mutagenic translesion synthesis.
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