JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites

Author(s): Yanhua MU, Jinhua HAN, Mingjie WU, Zongfang LI, Ke DU, Yameng WEI, Mengjie WU, Jun HUANG
Affiliation(s): National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China; more
Corresponding email(s): jhuang@zju.edu.cn, wumengjie@zju.edu.cn
Key Words: Genome instability; DNA double-strand breaks; homologous recombination; RAD51; Fibrillarin (FBL)

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Yanhua MU, Jinhua HAN, Mingjie WU, Zongfang LI, Ke DU, Yameng WEI, Mengjie WU, Jun HUANG. Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300518

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author="Yanhua MU, Jinhua HAN, Mingjie WU, Zongfang LI, Ke DU, Yameng WEI, Mengjie WU, Jun HUANG",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300518"
}

%0 Journal Article
%T Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites
%A Yanhua MU
%A Jinhua HAN
%A Mingjie WU
%A Zongfang LI
%A Ke DU
%A Yameng WEI
%A Mengjie WU
%A Jun HUANG
%J Journal of Zhejiang University SCIENCE B
%P 1165-1173
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2300518"

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T1 - Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites
A1 - Yanhua MU
A1 - Jinhua HAN
A1 - Mingjie WU
A1 - Zongfang LI
A1 - Ke DU
A1 - Yameng WEI
A1 - Mengjie WU
A1 - Jun HUANG
J0 - Journal of Zhejiang University Science B
SP - 1165
EP - 1173
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2300518"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).

纤维蛋白通过促进重组酶RAD51在DNA损伤位点的招募参与同源重组修复

慕艳华^1,2，韩金花³，邬明杰⁴，李宗芳¹，杜轲¹，魏雅萌¹，吴梦婕⁵，黄俊^3,6,7
¹西安交通大学第二附属医院生物诊断治疗国家地方联合工程研究中心，中国西安市，710004
²浙江大学生命科学研究院生命系统稳态与保护教育部重点实验室/细胞信号网络创新中心，中国杭州市，310058
³浙江省老年医学重点实验室/浙江省老年医学研究所/浙江医院老年病科，中国杭州市，310030
⁴浙江大学医学院第一附属医院创伤中心，中国杭州市，310003
⁵浙江大学医学院附属口腔医院/浙江省口腔生物医学研究重点实验室，中国杭州市，310006
⁶浙江大学生命科学研究院浙江省癌症分子细胞生物学重点实验室，中国杭州市，310058
⁷浙江大学医学院附属邵逸夫医院普通外科，中国杭州市，310016
摘要：同源重组（HR）是一种高度精确的DNA双链断裂（DSB）损伤修复方式。HR修复的关键步骤是重组酶RAD51通过包裹单链DNA形成核酸蛋白纤维丝，进行同源模板搜索，并进行DNA链入侵反应，从而启动DNA修复合成。本研究发现，纤维蛋白（FBL）是重要的HR调节因子。一旦发生DNA损伤，FBL就被招募到DSB位点，并直接与RAD51互作。细胞缺失FBL会导致RAD51在DNA损伤位点募集减少，HR修复效率降低。此外，细胞缺失FBL会导致染色体畸变增加，促使细胞对DNA损伤药物敏感。本研究提出了FBL介导的RAD51在DNA损伤位点的招募的新机制，并强调了FBL在癌症治疗中的潜在意义。

关键词组：基因组不稳定性；DNA双链断裂；同源重组；RAD51；纤维蛋白

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Reference

[1]BluntT, FinnieNJ, TaccioliGE, et al., 1995. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell, 80(5):813-823.

[2]CanelaA, MamanY, JungS, et al., 2017. Genome organization drives chromosome fragility. Cell, 170(3):507-521.e18.

[3]HanahanD, 2022. Hallmarks of cancer: new dimensions. Cancer Discov, 12(1):31-46.

[4]HartleyKO, GellD, SmithGCM, et al., 1995. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell, 82(5):849-856.

[5]HilarioJ, AmitaniI, BaskinRJ, et al., 2009. Direct imaging of human Rad51 nucleoprotein dynamics on individual DNA molecules. Proc Natl Acad Sci USA, 106(2):361-368.

[6]KatsukiY, JeggoPA, UchiharaY, et al., 2020. DNA double-strand break end resection: a critical relay point for determining the pathway of repair and signaling. Genome Instab Dis, 1(4):155-171.

[7]LiYH, YuanJ, 2021. Role of deubiquitinating enzymes in DNA double-strand break repair. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(1):63-72.

[8]MaCJ, GibbB, KwonY, et al., 2017. Protein dynamics of human RPA and RAD51 on ssDNA during assembly and disassembly of the RAD51 filament. Nucleic Acids Res, 45(2):749-761.

[9]MarcelV, GhayadSE, BelinS, et al., 2013. p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer. Cancer Cell, 24(3):318-330.

[10]MinéJ, DisseauL, TakahashiM, et al., 2007. Real-time measurements of the nucleation, growth and dissociation of single Rad51-DNA nucleoprotein filaments. Nucleic Acids Res, 35(21):7171-7187.

[11]NewtonK, PetfalskiE, TollerveyD, et al., 2003. Fibrillarin is essential for early development and required for accumulation of an intron-encoded small nucleolar RNA in the mouse. Mol Cell Biol, 23(23):8519-8527.

[12]OmerAD, ZiescheS, EbhardtH, et al., 2002. In vitro reconstitution and activity of a C/D box methylation guide ribonucleoprotein complex. Proc Natl Acad Sci USA, 99(8):5289-5294.

[13]SchimmangT, TollerveyD, KernH, et al., 1989. A yeast nucleolar protein related to mammalian fibrillarin is associated with small nucleolar RNA and is essential for viability. EMBO J, 8(13):4015-4024.

[14]ShinoharaA, OgawaH, OgawaT, 1992. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell, 69(3):457-470.

[15]SnaarS, WiesmeijerK, JochemsenAG, et al., 2000. Mutational analysis of fibrillarin and its mobility in living human cells. J Cell Biol, 151(3):653-662.

[16]TessarzP, Santos-RosaH, RobsonSC, et al., 2014. Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification. Nature, 505(7484):564-568.

[17]TikuV, JainC, RazY, et al., 2017. Small nucleoli are a cellular hallmark of longevity. Nat Commun, 8:16083.

[18]TollerveyD, LehtonenH, JansenR, et al., 1993. Temperature-sensitive mutations demonstrate roles for yeast fibrillarin in pre-rRNA processing, pre-rRNA methylation, and ribosome assembly. Cell, 72(3):443-457.

[19]XiangZY, LiuH, HuY, 2023. DNA damage repair and cancer immunotherapy. Genome Instab Dis, 4(4):210-226.

[20]YiYH, MaTH, LeeLW, et al., 2015. A genetic cascade of let-7-ncl-1-fib-1 modulates nucleolar size and rRNA pool in Caenorhabditis elegans. PLoS Genet, 11(10):e1005580.

[21]YoshikawaH, KomatsuW, HayanoT, et al., 2011. Splicing factor 2-associated protein p32 participates in ribosome biogenesis by regulating the binding of Nop52 and fibrillarin to preribosome particles. Mol Cell Proteomics, 10(8):M110.006148.

[22]ZhangF, GongZH, 2021. Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(1):38-46.

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纤维蛋白通过促进重组酶RAD51在DNA损伤位点的招募参与同源重组修复

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