在DNA双链断裂附近将基因切换至沉默模式。
Switching genes to silent mode near DNA double-strand breaks.
作者信息
Polo Sophie E
机构信息
Epigenetics & Cell Fate Centre, UMR7216 CNRS, Sorbonne Paris Cité, Paris Diderot University, Paris, France.
出版信息
EMBO Rep. 2017 May;18(5):659-660. doi: 10.15252/embr.201744052. Epub 2017 Mar 23.
Abstract
Transcription is tightly regulated in response to DNA damage. Rapid and transient pausing of RNA polymerase II (RNAPII) is indeed critical to restrict the production of aberrant transcripts from damaged loci and to prevent deleterious collisions between transcription and repair machineries. Yet, how DNA lesions signal to the transcription machinery to coordinate DNA repair with transcriptional silencing is not fully elucidated. In this issue of , Awwad 1 bring a new piece to the puzzle by identifying the negative transcription elongation factor NELF as a critical player in this process. They demonstrate that NELF is recruited to DNA double‐strand breaks (DSBs) near transcriptionally active genes in a poly(ADP‐ribose)‐ and RNAPII‐dependent manner to promote transcriptional repression and facilitate DSB repair.
摘要
转录过程受到严格调控以应对DNA损伤。RNA聚合酶II（RNAPII）的快速短暂暂停对于限制受损基因座异常转录本的产生以及防止转录与修复机制之间的有害碰撞至关重要。然而，DNA损伤如何向转录机制发出信号以协调DNA修复与转录沉默尚未完全阐明。在本期杂志中，Awwad等人通过鉴定负转录延伸因子NELF作为这一过程中的关键参与者，为这一谜题增添了新的内容。他们证明，NELF以聚（ADP-核糖）和RNAPII依赖的方式被招募到转录活跃基因附近的DNA双链断裂（DSB）处，以促进转录抑制并促进DSB修复。
相似文献
1
Switching genes to silent mode near DNA double-strand breaks.在DNA双链断裂附近将基因切换至沉默模式。
EMBO Rep. 2017 May;18(5):659-660. doi: 10.15252/embr.201744052. Epub 2017 Mar 23.
2
Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors.单细胞微阵列技术可实现高通量评估 DNA 双链断裂和 DNA 修复抑制剂。
Cell Cycle. 2013 Mar 15;12(6):907-15. doi: 10.4161/cc.23880. Epub 2013 Feb 19.
3
Efficient repair of bleomycin-induced double-strand breaks in barley ribosomal genes.博来霉素诱导的大麦核糖体基因双链断裂的高效修复
Mutat Res. 2006 Oct 10;601(1-2):179-90. doi: 10.1016/j.mrfmmm.2006.07.004. Epub 2006 Aug 22.
4
Imaging DNA double-strand breaks - are we there yet?成像DNA双链断裂——我们做到了吗？
Nat Rev Mol Cell Biol. 2022 Sep;23(9):579-580. doi: 10.1038/s41580-022-00513-7.
5
Roles of ATM and ATR in DNA double strand breaks and replication stress.ATM 和 ATR 在 DNA 双链断裂和复制应激中的作用。
Prog Biophys Mol Biol. 2021 Aug;163:109-119. doi: 10.1016/j.pbiomolbio.2021.03.007. Epub 2021 Apr 20.
6
MTE1 Functions with MPH1 in Double-Strand Break Repair.MTE1在双链断裂修复中与MPH1共同发挥作用。
Genetics. 2016 May;203(1):147-57. doi: 10.1534/genetics.115.185454. Epub 2016 Feb 26.
7
Protein ADP-ribosylation and the cellular response to DNA strand breaks.蛋白质 ADP 核糖基化与细胞对 DNA 链断裂的反应。
DNA Repair (Amst). 2014 Jul;19:108-13. doi: 10.1016/j.dnarep.2014.03.021. Epub 2014 Apr 20.
8
Transcriptional regulation and chromatin dynamics at DNA double-strand breaks.DNA 双链断裂处的转录调控和染色质动力学。
Exp Mol Med. 2022 Oct;54(10):1705-1712. doi: 10.1038/s12276-022-00862-5. Epub 2022 Oct 13.
9
DNA Double Strand Breaks Repair Inhibitors: Relevance as Potential New Anticancer Therapeutics.DNA 双链断裂修复抑制剂：作为潜在新型抗癌治疗药物的相关性。
Curr Med Chem. 2019;26(8):1483-1493. doi: 10.2174/0929867325666180214113154.
10
Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends.Ku 是一种 5'-dRP/AP 核酸内切酶，可切除断裂末端附近的核苷酸损伤。
Nature. 2010 Apr 22;464(7292):1214-7. doi: 10.1038/nature08926. Epub 2010 Apr 11.
引用本文的文献
1
Update on R-loops in genomic integrity: Formation, functions, and implications for human diseases.基因组完整性中R环的最新进展：形成、功能及其对人类疾病的影响
Genes Dis. 2024 Aug 30;12(4):101401. doi: 10.1016/j.gendis.2024.101401. eCollection 2025 Jul.
2
Lysine Crotonylation: An Emerging Player in DNA Damage Response.赖氨酸丁烯酰化：DNA 损伤反应中的新兴参与者。
Biomolecules. 2022 Oct 5;12(10):1428. doi: 10.3390/biom12101428.
3
Phasor histone FLIM-FRET microscopy quantifies spatiotemporal rearrangement of chromatin architecture during the DNA damage response.相量组蛋白 FLIM-FRET 显微镜定量分析了 DNA 损伤反应过程中染色质结构的时空重排。
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7323-7332. doi: 10.1073/pnas.1814965116. Epub 2019 Mar 27.
4
HDAC-dependent decrease in histone crotonylation during DNA damage.DNA损伤期间组蛋白巴豆酰化依赖于HDAC的减少。
J Mol Cell Biol. 2019 Sep 19;11(9):804-806. doi: 10.1093/jmcb/mjz019.
本文引用的文献
1
NELF-E is recruited to DNA double-strand break sites to promote transcriptional repression and repair.NELF-E被招募到DNA双链断裂位点，以促进转录抑制和修复。
EMBO Rep. 2017 May;18(5):745-764. doi: 10.15252/embr.201643191. Epub 2017 Mar 23.
2
Transcription and DNA Damage: Holding Hands or Crossing Swords?转录与 DNA 损伤：携手合作还是针锋相对？
J Mol Biol. 2017 Oct 27;429(21):3215-3229. doi: 10.1016/j.jmb.2016.11.002. Epub 2016 Nov 5.
3
Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation.聚（ADP-核糖）聚合酶（PARP）靶点的化学遗传学发现揭示了PARP-1在转录延伸中的作用。
Science. 2016 Jul 1;353(6294):45-50. doi: 10.1126/science.aaf7865. Epub 2016 Jun 2.
4
Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair.ATM 磷酸化的转录延伸因子 ENL 招募多梳蛋白并关闭 DSB 修复的转录。
Mol Cell. 2015 May 7;58(3):468-82. doi: 10.1016/j.molcel.2015.03.023. Epub 2015 Apr 23.
5
Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination.筛查鉴定出在促进同源重组的转录相关DNA损伤的染色质识别中起作用的溴结构域蛋白ZMYND8。
Genes Dev. 2015 Jan 15;29(2):197-211. doi: 10.1101/gad.252189.114.
6
Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin.在染色质活跃转录区域的DNA断裂处进行转录抑制和修复时对PBAF的需求。
Mol Cell. 2014 Sep 4;55(5):723-32. doi: 10.1016/j.molcel.2014.06.028. Epub 2014 Jul 24.
7
DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks.DNA-PKcs 依赖性 RNA 聚合酶 II 在 DNA 断裂存在时转录的停滞。
Nat Struct Mol Biol. 2012 Feb 12;19(3):276-82. doi: 10.1038/nsmb.2224.
8
A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage.染色质定位筛选揭示了聚（ADP 核糖）调节的抑制性多梳和 NuRD 复合物在 DNA 损伤部位的募集。
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18475-80. doi: 10.1073/pnas.1012946107. Epub 2010 Oct 11.
9
ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks.ATM 依赖性染色质变化使 DNA 双链断裂顺式转录沉默。
Cell. 2010 Jun 11;141(6):970-81. doi: 10.1016/j.cell.2010.04.038.
10
NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation.NELF是一种包含RD的多亚基复合物，它与DSIF协同作用以抑制RNA聚合酶II的延伸。
Cell. 1999 Apr 2;97(1):41-51. doi: 10.1016/s0092-8674(00)80713-8.
Zotero 插件