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绘制免疫球蛋白类别转换重组的 DNA 修复路线图。

Charting a DNA Repair Roadmap for Immunoglobulin Class Switch Recombination.

机构信息

Laboratory of Genome Diversification and Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.

Laboratory of Genome Diversification and Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.

出版信息

Trends Biochem Sci. 2021 Mar;46(3):184-199. doi: 10.1016/j.tibs.2020.10.005. Epub 2020 Nov 26.

Abstract

Immunoglobulin (Ig) class switch recombination (CSR) is the process occurring in mature B cells that diversifies the effector component of antibody responses. CSR is initiated by the activity of the B cell-specific enzyme activation-induced cytidine deaminase (AID), which leads to the formation of programmed DNA double-strand breaks (DSBs) at the Ig heavy chain (Igh) locus. Mature B cells use a multilayered and complex regulatory framework to ensure that AID-induced DNA breaks are channeled into productive repair reactions leading to CSR, and to avoid aberrant repair events causing lymphomagenic chromosomal translocations. Here, we review the DNA repair pathways acting on AID-induced DSBs and their functional interplay, with a particular focus on the latest developments in their molecular composition and mechanistic regulation.

摘要

免疫球蛋白 (Ig) 类别转换重组 (CSR) 是成熟 B 细胞中发生的过程,可使抗体反应的效应子成分多样化。CSR 是由 B 细胞特异性酶激活诱导胞嘧啶脱氨酶 (AID) 的活性引发的,该酶导致 Ig 重链 (Igh) 基因座处形成程序性 DNA 双链断裂 (DSB)。成熟 B 细胞使用多层且复杂的调控框架,以确保 AID 诱导的 DNA 断裂被引导至产生 CSR 的有效修复反应,并避免导致淋巴瘤发生的染色体易位的异常修复事件。在这里,我们综述了作用于 AID 诱导的 DSB 的 DNA 修复途径及其功能相互作用,特别关注其分子组成和机制调节的最新进展。

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