Southern Alberta Cancer Research Institute, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N4N1.
DNA Repair (Amst). 2011 Oct 10;10(10):1071-6. doi: 10.1016/j.dnarep.2011.07.012. Epub 2011 Aug 24.
53BP1 is an established player in the cellular response to DNA damage and is a canonical component of ionizing-radiation induced foci--that cadre of proteins which assemble at DNA double strand breaks following radiation exposure and which are readily visualized by immunofluorescence microscopy. While its roles in p53 regulation and cell cycle checkpoint activation have been studied for some time, the impact of 53BP1 on DNA double strand break rejoining has only come to light in the past few years. Convincing evidence now exists for 53BP1 significantly affecting the outcome of DNA double strand break repair in several contexts, many of which hint to an important role in modulating chromatin structure surrounding the break site. Here, we highlight the known and emerging roles of 53BP1 in DNA double strand break repair, including the repair of lesions induced within heterochromatin, following telomere uncapping, in long-range V(D)J recombination, during immunoglobulin class switch recombination and its much debated role in regulating resection during homologous recombination.
53BP1 是细胞对 DNA 损伤反应中的一个既定参与者，也是电离辐射诱导焦点的典型组成部分——在辐射暴露后，这组蛋白质聚集在 DNA 双链断裂处，通过免疫荧光显微镜很容易观察到。虽然其在 p53 调节和细胞周期检查点激活中的作用已经研究了一段时间，但 53BP1 对 DNA 双链断裂重连的影响仅在过去几年才被发现。现在有令人信服的证据表明，53BP1 在多种情况下显著影响 DNA 双链断裂修复的结果，其中许多证据表明其在调节断裂部位周围染色质结构方面发挥着重要作用。在这里，我们重点介绍 53BP1 在 DNA 双链断裂修复中的已知和新兴作用，包括修复异染色质内诱导的损伤、端粒去帽后、长距离 V(D)J 重组、免疫球蛋白类别转换重组以及其在同源重组中调控切除过程的备受争议的作用。
