Lac 操纵子重复可在哺乳动物细胞中产生可追踪的脆性位点。
Lac operator repeats generate a traceable fragile site in mammalian cells.
机构信息
Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
出版信息
EMBO Rep. 2011 Sep 30;12(10):1032-8. doi: 10.1038/embor.2011.158.
Abstract
One limitation for the study of chromosomal fragile sites is that they must be studied on metaphase spreads, after the breakage. We show here that bacterial lac operator (lacO) repeats are prone to spontaneous breakage, which when combined with a fluorescent lac repressor (lacR) has allowed us to track a fragile site through the cell cycle. By using this system, we show that Plk1-interacting checkpoint helicase (PICH) is already present at fragile sites during interphase, suggesting roles for this helicase beyond mitosis. In addition, we report that the oncogene Myc promotes the formation of anaphase bridges and micronuclei containing fragile-site sequences.
摘要
该研究存在一个局限性，即必须在染色体断裂后通过中期分裂来研究脆性位点。我们在此表明，细菌 lac 操纵子（lacO）重复序列容易自发断裂，而与荧光 lac 阻遏物（lacR）结合后，我们就可以在细胞周期中追踪脆性位点。通过使用该系统，我们表明 Plk1 相互作用的检查点解旋酶（PICH）在有丝分裂间期已经存在于脆性位点，这表明该解旋酶的作用超出了有丝分裂。此外，我们还报告说致癌基因 Myc 促进了含有脆性位点序列的后期桥和微核的形成。
相似文献
1
Lac operator repeats generate a traceable fragile site in mammalian cells.Lac 操纵子重复可在哺乳动物细胞中产生可追踪的脆性位点。
EMBO Rep. 2011 Sep 30;12(10):1032-8. doi: 10.1038/embor.2011.158.
2
Inhibition of topoisomerase I prevents chromosome breakage at common fragile sites.抑制拓扑异构酶 I 可防止常见脆性位点的染色体断裂。
DNA Repair (Amst). 2010 Jun 4;9(6):678-89. doi: 10.1016/j.dnarep.2010.03.005. Epub 2010 Apr 21.
3
DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells.脆性位点的 DNA 断裂会在人类甲状腺细胞中产生致癌性的 RET/PTC 重排。
Oncogene. 2010 Apr 15;29(15):2272-80. doi: 10.1038/onc.2009.502. Epub 2010 Jan 25.
4
Dicentric chromosome stretching during anaphase reveals roles of Sir2/Ku in chromatin compaction in budding yeast.后期双着丝粒染色体拉伸揭示了Sir2/Ku在芽殖酵母染色质压缩中的作用。
Mol Biol Cell. 2001 Sep;12(9):2800-12. doi: 10.1091/mbc.12.9.2800.
5
Origin of the asymmetrical contact between lac repressor and lac operator DNA.乳糖阻遏蛋白与乳糖操纵基因DNA之间不对称接触的起源。
J Mol Biol. 1993 Oct 5;233(3):389-99. doi: 10.1006/jmbi.1993.1519.
6
Evidence for a contact between glutamine-18 of lac repressor and base pair 7 of lac operator.乳糖阻遏蛋白的谷氨酰胺-18与乳糖操纵基因的碱基对7之间存在接触的证据。
Proc Natl Acad Sci U S A. 1986 Jan;83(2):303-7. doi: 10.1073/pnas.83.2.303.
7
Tagging the genome of the murine leukemia retrovirus SL3-3 by a bacterial lac operator sequence.通过细菌乳糖操纵子序列对鼠白血病逆转录病毒SL3-3的基因组进行标记。
Gene. 1991 Dec 30;109(2):243-7. doi: 10.1016/0378-1119(91)90615-i.
8
FRA18C: a new aphidicolin-inducible fragile site on chromosome 18q22, possibly associated with in vivo chromosome breakage.FRA18C：18号染色体q22上一个新的阿非科林诱导型脆性位点，可能与体内染色体断裂有关。
J Med Genet. 2007 May;44(5):347-52. doi: 10.1136/jmg.2006.044628.
9
Direct cloning of DNA sequences from the common fragile site region at chromosome band 3p14.2.直接克隆来自染色体3p14.2带区常见脆性位点区域的DNA序列。
Genomics. 1996 Jul 1;35(1):109-17. doi: 10.1006/geno.1996.0329.
10
Chromosomal expression and localization of aphidicolin-induced fragile sites in the standard karyotype of river buffalo (Bubalus bubalis).水牛（Bubalus bubalis）标准核型中阿非科林诱导的脆性位点的染色体表达与定位。
Cytogenet Genome Res. 2008;120(1-2):178-82. doi: 10.1159/000118760. Epub 2008 Apr 30.
引用本文的文献
1
repeat expansion creates the unstable folate-sensitive fragile site FRA9A.重复扩增产生不稳定的叶酸敏感脆性位点FRA9A。
NAR Mol Med. 2024 Nov 12;1(4):ugae019. doi: 10.1093/narmme/ugae019. eCollection 2024 Oct.
2
Tracking pairwise genomic loci by the ParB-ParS and Noc-NBS systems in living cells.在活细胞中通过 ParB-ParS 和 Noc-NBS 系统跟踪成对的基因组基因座。
Nucleic Acids Res. 2024 May 22;52(9):4922-4934. doi: 10.1093/nar/gkae134.
3
Live cell imaging of DNA and RNA with fluorescent signal amplification and background reduction techniques.运用荧光信号放大和背景降低技术对DNA和RNA进行活细胞成像。
Front Cell Dev Biol. 2023 Jun 5;11:1216232. doi: 10.3389/fcell.2023.1216232. eCollection 2023.
4
Targeted assembly of ectopic kinetochores to induce chromosome-specific segmental aneuploidies.靶向组装异位着丝粒以诱导染色体特异性片段非整倍体。
EMBO J. 2023 May 15;42(10):e111587. doi: 10.15252/embj.2022111587. Epub 2023 Apr 17.
5
A kinesin-based approach for inducing chromosome-specific mis-segregation in human cells.基于驱动蛋白的方法诱导人细胞中染色体特异性错误分离。
EMBO J. 2023 May 15;42(10):e111559. doi: 10.15252/embj.2022111559. Epub 2023 Apr 11.
6
Visualizing the Genome: Experimental Approaches for Live-Cell Chromatin Imaging.可视化基因组：活细胞染色质成像的实验方法。
Cells. 2022 Dec 16;11(24):4086. doi: 10.3390/cells11244086.
7
Fragile sites, chromosomal lesions, tandem repeats, and disease.脆性位点、染色体病变、串联重复序列与疾病。
Front Genet. 2022 Nov 17;13:985975. doi: 10.3389/fgene.2022.985975. eCollection 2022.
8
PICH acts as a force-dependent nucleosome remodeler.PICH 作为一种力依赖性核小体重塑酶。
Nat Commun. 2022 Nov 25;13(1):7277. doi: 10.1038/s41467-022-35040-8.
9
DNA damage responses that enhance resilience to replication stress.增强复制应激抗性的 DNA 损伤反应。
Cell Mol Life Sci. 2021 Nov;78(21-22):6763-6773. doi: 10.1007/s00018-021-03926-3. Epub 2021 Aug 31.
10
Alternative lengthening of telomeres is a self-perpetuating process in ALT-associated PML bodies.端粒的替代性延长是 ALT 相关的 PML 体中自我维持的过程。
Mol Cell. 2021 Mar 4;81(5):1027-1042.e4. doi: 10.1016/j.molcel.2020.12.030. Epub 2021 Jan 15.
本文引用的文献
1
Studies of genomic copy number changes in human cancers reveal signatures of DNA replication stress.人类癌症中基因组拷贝数变化的研究揭示了 DNA 复制应激的特征。
Mol Oncol. 2011 Aug;5(4):308-14. doi: 10.1016/j.molonc.2011.05.002. Epub 2011 May 20.
2
Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier.复制叉障碍诱导的超细后期桥、断裂的 DNA 和不合法重组。
Nucleic Acids Res. 2011 Aug;39(15):6568-84. doi: 10.1093/nar/gkr340. Epub 2011 May 16.
3
Common fragile sites are characterized by histone hypoacetylation.常见脆弱位点的特点是组蛋白低度乙酰化。
Hum Mol Genet. 2009 Dec 1;18(23):4501-12. doi: 10.1093/hmg/ddp410. Epub 2009 Aug 28.
4
Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice.由TRF1缺乏导致的端粒脆性增加和融合会致使小鼠出现退行性病变并增加患癌风险。
Genes Dev. 2009 Sep 1;23(17):2060-75. doi: 10.1101/gad.543509. Epub 2009 Aug 13.
5
Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication.哺乳动物端粒类似于脆性位点，高效复制需要TRF1。
Cell. 2009 Jul 10;138(1):90-103. doi: 10.1016/j.cell.2009.06.021.
6
Replication stress induces sister-chromatid bridging at fragile site loci in mitosis.复制应激在有丝分裂过程中诱导脆弱位点处的姐妹染色单体桥接。
Nat Cell Biol. 2009 Jun;11(6):753-60. doi: 10.1038/ncb1882. Epub 2009 May 24.
7
The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities.范可尼贫血（FANC）通路与布卢姆综合征蛋白（BLM）在有丝分裂过程中协同作用，以防止微核形成和染色体异常。
Nat Cell Biol. 2009 Jun;11(6):761-8. doi: 10.1038/ncb1883. Epub 2009 May 24.
8
Facilitating replication under stress: an oncogenic function of MYC?在应激条件下促进复制：MYC的一种致癌功能？
Nat Rev Cancer. 2009 Jun;9(6):441-4. doi: 10.1038/nrc2640.
9
Activation of the cellular DNA damage response in the absence of DNA lesions.在无DNA损伤情况下细胞DNA损伤反应的激活。
Science. 2008 Jun 13;320(5882):1507-10. doi: 10.1126/science.1159051. Epub 2008 May 15.
10
An oncogene-induced DNA damage model for cancer development.一种用于癌症发展的癌基因诱导DNA损伤模型。
Science. 2008 Mar 7;319(5868):1352-5. doi: 10.1126/science.1140735.
Zotero 插件