IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47936-8.html
   My bibliography  Save this article

Mechanism of DNA unwinding by MCM8-9 in complex with HROB

Author

Listed:
  • Ananya Acharya

    (Faculty of Biomedical Sciences
    Eidgenössische Technische Hochschule (ETH))

  • Hélène Bret

    (Institute for Integrative Biology of the Cell (I2BC))

  • Jen-Wei Huang

    (Columbia University Irving Medical Center)

  • Martin Mütze

    (Universität Leipzig)

  • Martin Göse

    (Universität Leipzig)

  • Vera Maria Kissling

    (Eidgenössische Technische Hochschule (ETH)
    Swiss Federal Laboratories for Materials Science and Technology (Empa))

  • Ralf Seidel

    (Universität Leipzig)

  • Alberto Ciccia

    (Columbia University Irving Medical Center)

  • Raphaël Guérois

    (Institute for Integrative Biology of the Cell (I2BC))

  • Petr Cejka

    (Faculty of Biomedical Sciences
    Eidgenössische Technische Hochschule (ETH))

Abstract

HROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity. MCM8-9-HROB prefer branched DNA structures, and display low DNA unwinding processivity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in the presence of ATP. The hexamer involves two repeating protein-protein interfaces between the alternating MCM8 and MCM9 subunits. One of these interfaces is quite stable and forms an obligate heterodimer across which HROB binds. The other interface is labile and mediates hexamer assembly, independently of HROB. The ATPase site formed at the labile interface contributes disproportionally more to DNA unwinding than that at the stable interface. Here, we show that HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA.

Suggested Citation

  • Ananya Acharya & Hélène Bret & Jen-Wei Huang & Martin Mütze & Martin Göse & Vera Maria Kissling & Ralf Seidel & Alberto Ciccia & Raphaël Guérois & Petr Cejka, 2024. "Mechanism of DNA unwinding by MCM8-9 in complex with HROB," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47936-8
    DOI: 10.1038/s41467-024-47936-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47936-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47936-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    2. Martin Meagher & Leslie B. Epling & Eric J. Enemark, 2019. "DNA translocation mechanism of the MCM complex and implications for replication initiation," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Ananya Acharya & Kristina Kasaciunaite & Martin Göse & Vera Kissling & Raphaël Guérois & Ralf Seidel & Petr Cejka, 2021. "Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    4. Thomas C. R. Miller & Julia Locke & Julia F. Greiwe & John F. X. Diffley & Alessandro Costa, 2019. "Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM," Nature, Nature, vol. 575(7784), pages 704-710, November.
    5. Hazal B. Kose & Sherry Xie & George Cameron & Melania S. Strycharska & Hasan Yardimci, 2020. "Duplex DNA engagement and RPA oppositely regulate the DNA-unwinding rate of CMG helicase," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    6. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    7. Elda Cannavo & Aurore Sanchez & Roopesh Anand & Lepakshi Ranjha & Jannik Hugener & Céline Adam & Ananya Acharya & Nicolas Weyland & Xavier Aran-Guiu & Jean-Baptiste Charbonnier & Eva R. Hoffmann & Val, 2020. "Regulation of the MLH1–MLH3 endonuclease in meiosis," Nature, Nature, vol. 586(7830), pages 618-622, October.
    8. Jacob S. Lewis & Marta H. Gross & Joana Sousa & Sarah S. Henrikus & Julia F. Greiwe & Andrea Nans & John F. X. Diffley & Alessandro Costa, 2022. "Mechanism of replication origin melting nucleated by CMG helicase assembly," Nature, Nature, vol. 606(7916), pages 1007-1014, June.
    9. Kyung Yong Lee & Jun-Sub Im & Etsuko Shibata & Jonghoon Park & Naofumi Handa & Stephen C. Kowalczykowski & Anindya Dutta, 2015. "MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    10. Max E. Douglas & Ferdos Abid Ali & Alessandro Costa & John F. X. Diffley, 2018. "The mechanism of eukaryotic CMG helicase activation," Nature, Nature, vol. 555(7695), pages 265-268, March.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Giordano Reginato & Maria Rosaria Dello Stritto & Yanbo Wang & Jingzhou Hao & Raphael Pavani & Michael Schmitz & Swagata Halder & Vincent Morin & Elda Cannavo & Ilaria Ceppi & Stefan Braunshier & Anan, 2024. "HLTF disrupts Cas9-DNA post-cleavage complexes to allow DNA break processing," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Matthew Day & Bilal Tetik & Milena Parlak & Yasser Almeida-Hernández & Markus Räschle & Farnusch Kaschani & Heike Siegert & Anika Marko & Elsa Sanchez-Garcia & Markus Kaiser & Isabel A. Barker & Laure, 2024. "TopBP1 utilises a bipartite GINS binding mode to support genome replication," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Zhichun Xu & Jianrong Feng & Daqi Yu & Yunjing Huo & Xiaohui Ma & Wai Hei Lam & Zheng Liu & Xiang David Li & Toyotaka Ishibashi & Shangyu Dang & Yuanliang Zhai, 2023. "Synergism between CMG helicase and leading strand DNA polymerase at replication fork," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Jianbing Ma & Gangshun Yi & Mingda Ye & Craig MacGregor-Chatwin & Yuewen Sheng & Ying Lu & Ming Li & Qingrong Li & Dong Wang & Robert J. C. Gilbert & Peijun Zhang, 2024. "Open architecture of archaea MCM and dsDNA complexes resolved using monodispersed streptavidin affinity CryoEM," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Agata Butryn & Julia F. Greiwe & Alessandro Costa, 2025. "Unidirectional MCM translocation away from ORC drives origin licensing," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    5. Daniel Ramírez Montero & Humberto Sánchez & Edo Veen & Theo Laar & Belén Solano & John F. X. Diffley & Nynke H. Dekker, 2023. "Nucleotide binding halts diffusion of the eukaryotic replicative helicase during activation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Yue Wu & Qiongdan Zhang & Yuhan Lin & Wai Hei Lam & Yuanliang Zhai, 2024. "Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    7. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative Artificial Intelligence," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, pages 7-46, National Bureau of Economic Research, Inc.
    8. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    10. Shuo-Shuo Liu & Tian-Xia Jiang & Fan Bu & Ji-Lan Zhao & Guang-Fei Wang & Guo-Heng Yang & Jie-Yan Kong & Yun-Fan Qie & Pei Wen & Li-Bin Fan & Ning-Ning Li & Ning Gao & Xiao-Bo Qiu, 2024. "Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Zhao-Shan Chen & Hsiang-Chi Huang & Xiangkun Wang & Karin Schön & Yane Jia & Michael Lebens & Danica F. Besavilla & Janarthan R. Murti & Yanhong Ji & Aishe A. Sarshad & Guohua Deng & Qiyun Zhu & David, 2025. "Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    12. Sourav Nayak & Thomas J. Peto & Michal Kucharski & Rupam Tripura & James J. Callery & Duong Tien Quang Huy & Mathieu Gendrot & Dysoley Lek & Ho Dang Trung Nghia & Rob W. Pluijm & Nguyen Dong & Le Than, 2024. "Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Xiaoke Yang & Mingqi Zhu & Xue Lu & Yuxin Wang & Junyu Xiao, 2024. "Architecture and activation of human muscle phosphorylase kinase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    14. Efren Garcia-Maldonado & Andrew D. Huber & Sergio C. Chai & Stanley Nithianantham & Yongtao Li & Jing Wu & Shyaron Poudel & Darcie J. Miller & Jayaraman Seetharaman & Taosheng Chen, 2024. "Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Kristy Rochon & Brianna L. Bauer & Nathaniel A. Roethler & Yuli Buckley & Chih-Chia Su & Wei Huang & Rajesh Ramachandran & Maria S. K. Stoll & Edward W. Yu & Derek J. Taylor & Jason A. Mears, 2024. "Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    16. Katherine A. Ray & Joshua D. Lutgens & Ramesh Bista & Jie Zhang & Ronak R. Desai & Melissa Hirsch & Takeshi Miyazawa & Antonio Cordova & Adrian T. Keatinge-Clay, 2024. "Assessing and harnessing updated polyketide synthase modules through combinatorial engineering," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Fan Lu & Liang Zhu & Thomas Bromberger & Jun Yang & Qiannan Yang & Jianmin Liu & Edward F. Plow & Markus Moser & Jun Qin, 2022. "Mechanism of integrin activation by talin and its cooperation with kindlin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Zengyu Shao & Jiuwei Lu & Nelli Khudaverdyan & Jikui Song, 2024. "Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    19. Yudong Gao & Daichi Shonai & Matthew Trn & Jieqing Zhao & Erik J. Soderblom & S. Alexandra Garcia-Moreno & Charles A. Gersbach & William C. Wetsel & Geraldine Dawson & Dmitry Velmeshev & Yong-hui Jian, 2024. "Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Martin F. Peter & Christian Gebhardt & Rebecca Mächtel & Gabriel G. Moya Muñoz & Janin Glaenzer & Alessandra Narducci & Gavin H. Thomas & Thorben Cordes & Gregor Hagelueken, 2022. "Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47936-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.