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持续的 DNA 损伤信号和 DNA 聚合酶θ促进了断裂染色体的分离。

Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation.

机构信息

Department of Cell Biology, Duke University School of Medicine, Durham, NC.

Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC.

出版信息

J Cell Biol. 2021 Dec 6;220(12). doi: 10.1083/jcb.202106116. Epub 2021 Oct 6.

DOI:10.1083/jcb.202106116
PMID:34613334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8500225/
Abstract

Cycling cells must respond to DNA double-strand breaks (DSBs) to avoid genome instability. Missegregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incompletely understood. We previously showed that Drosophilamelanogaster papillar cells lack DSB checkpoints (as observed in many cancer cells). Here, we show that papillar cells still recruit early acting repair machinery (Mre11 and RPA3) and the Fanconi anemia (FA) protein Fancd2 to DSBs. These proteins persist as foci on DSBs as cells enter mitosis. Repair foci are resolved in a stepwise manner during mitosis. DSB repair kinetics depends on both monoubiquitination of Fancd2 and the alternative end-joining protein DNA polymerase θ. Disruption of either or both of these factors causes micronuclei after DNA damage, which disrupts intestinal organogenesis. This study reveals a mechanism for how cells with inactive DSB checkpoints can respond to DNA damage that persists into mitosis.

摘要

循环细胞必须对 DNA 双链断裂 (DSBs) 作出反应，以避免基因组不稳定。有丝分裂过程中带有 DSB 的染色体错误分离会导致微核，这是与疾病相关的异常结构。细胞在有丝分裂过程中如何应对 DSB 尚不完全清楚。我们之前曾表明，果蝇的乳头状细胞缺乏 DSB 检查点（如许多癌细胞中观察到的那样）。在这里，我们表明乳头状细胞仍然会招募早期作用的修复机制（Mre11 和 RPA3）和范可尼贫血（FA）蛋白 Fancd2 到 DSB 上。随着细胞进入有丝分裂，这些蛋白质作为焦点持续存在于 DSB 上。在有丝分裂过程中，修复焦点以逐步的方式解决。DSB 修复动力学取决于 Fancd2 的单泛素化和替代末端连接蛋白 DNA 聚合酶θ。这两种因素中的任何一种或两种的破坏都会在 DNA 损伤后导致微核，从而破坏肠道器官发生。这项研究揭示了一种机制，即无活性 DSB 检查点的细胞如何对持续到有丝分裂的 DNA 损伤作出反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/cdb907aed813/JCB_202106116_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/35a43ee1a441/JCB_202106116_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/87321170d89b/JCB_202106116_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/d37961d2d7d9/JCB_202106116_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/e82d306262f6/JCB_202106116_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/818cce8f7106/JCB_202106116_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/44d25ec0a7cc/JCB_202106116_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/6af7994ae8a5/JCB_202106116_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/ad0004d9d064/JCB_202106116_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/22db84e34887/JCB_202106116_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/cdb907aed813/JCB_202106116_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/35a43ee1a441/JCB_202106116_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/87321170d89b/JCB_202106116_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/d37961d2d7d9/JCB_202106116_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/e82d306262f6/JCB_202106116_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/818cce8f7106/JCB_202106116_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/44d25ec0a7cc/JCB_202106116_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/6af7994ae8a5/JCB_202106116_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/ad0004d9d064/JCB_202106116_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/22db84e34887/JCB_202106116_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a177/8500225/cdb907aed813/JCB_202106116_Fig7.jpg

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2
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Elife. 2020 Oct 14;9:e58107. doi: 10.7554/eLife.58107.
3
Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks.促进同源定向修复选择的方法以应对 CRISPR/Cas9 诱导的双链断裂。
Genes (Basel). 2024 Jan 14;15(1):96. doi: 10.3390/genes15010096.
4
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis.Polθ 通过 PLK1 的磷酸化来修复有丝分裂中的双链断裂。
Nature. 2023 Sep;621(7978):415-422. doi: 10.1038/s41586-023-06506-6. Epub 2023 Sep 6.
5
Mitotic tethering enables inheritance of shattered micronuclear chromosomes.有丝分裂束缚使破碎的微核染色体能够遗传。
Nature. 2023 Jun;618(7967):1049-1056. doi: 10.1038/s41586-023-06216-z. Epub 2023 Jun 14.
6
Mitotic clustering of pulverized chromosomes from micronuclei.粉碎微核染色体的有丝分裂聚类。
Nature. 2023 Jun;618(7967):1041-1048. doi: 10.1038/s41586-023-05974-0. Epub 2023 May 10.
7
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8
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