Regulation of Precise DNA Repair by Nuclear Actin Polymerization: A Chance for Improving Gene Therapy?

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 Jul 12

PMID 38994946

Authors

Xiubin He

Cord Brakebusch

Affiliations

Soon will be listed here.

Abstract

Although more difficult to detect than in the cytoplasm, it is now clear that actin polymerization occurs in the nucleus and that it plays a role in the specific processes of the nucleus such as transcription, replication, and DNA repair. A number of studies suggest that nuclear actin polymerization is promoting precise DNA repair by homologous recombination, which could potentially be of help for precise genome editing and gene therapy. This review summarizes the findings and describes the challenges and chances in the field.

Citing Articles

Comparative response mechanisms of two cultivars of to f.sp. infection.

Duan Y, Jia Z, Lu Z, Hu H, Zhan R Front Plant Sci. 2025; 15():1492711.

PMID: 39850207 PMC: 11754190. DOI: 10.3389/fpls.2024.1492711.

Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor.

Jiang X, Mohapatra P, Rossing M, Zheng W, Zbodakova O, Thatte J Cells. 2025; 14(1.

PMID: 39791760 PMC: 11720165. DOI: 10.3390/cells14010059.

Bioinformatic Analysis of Actin-Binding Proteins in the Nucleolus During Heat Shock.

Taniguchi S, Torii T, Goto T, Takeuchi K, Katsumi R, Sumida M Genes (Basel). 2025; 15(12.

PMID: 39766847 PMC: 11675300. DOI: 10.3390/genes15121580.

References

Iacovoni J, Caron P, Lassadi I, Nicolas E, Massip L, Trouche D . High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome. EMBO J. 2010; 29(8):1446-57. PMC: 2868577. DOI: 10.1038/emboj.2010.38. View

Lamm N, Read M, Nobis M, Van Ly D, Page S, Masamsetti V . Nuclear F-actin counteracts nuclear deformation and promotes fork repair during replication stress. Nat Cell Biol. 2020; 22(12):1460-1470. DOI: 10.1038/s41556-020-00605-6. View

Ding B, Narvaez-Ortiz H, Singh Y, Hocky G, Chowdhury S, Nolen B . Structure of Arp2/3 complex at a branched actin filament junction resolved by single-particle cryo-electron microscopy. Proc Natl Acad Sci U S A. 2022; 119(22):e2202723119. PMC: 9295785. DOI: 10.1073/pnas.2202723119. View

Hofmann W, Stojiljkovic L, Fuchsova B, Vargas G, Mavrommatis E, Philimonenko V . Actin is part of pre-initiation complexes and is necessary for transcription by RNA polymerase II. Nat Cell Biol. 2004; 6(11):1094-101. DOI: 10.1038/ncb1182. View

Sage E, Shikazono N . Radiation-induced clustered DNA lesions: Repair and mutagenesis. Free Radic Biol Med. 2016; 107:125-135. DOI: 10.1016/j.freeradbiomed.2016.12.008. View

Amaral N, Ryu T, Li X, Chiolo I . Nuclear Dynamics of Heterochromatin Repair. Trends Genet. 2017; 33(2):86-100. PMC: 5285325. DOI: 10.1016/j.tig.2016.12.004. View

Locatelli M, Lawrimore J, Lin H, Sanaullah S, Seitz C, Segall D . DNA damage reduces heterogeneity and coherence of chromatin motions. Proc Natl Acad Sci U S A. 2022; 119(29):e2205166119. PMC: 9304018. DOI: 10.1073/pnas.2205166119. View

Ranjha L, Howard S, Cejka P . Main steps in DNA double-strand break repair: an introduction to homologous recombination and related processes. Chromosoma. 2018; 127(2):187-214. DOI: 10.1007/s00412-017-0658-1. View

Baarlink C, Plessner M, Sherrard A, Morita K, Misu S, Virant D . A transient pool of nuclear F-actin at mitotic exit controls chromatin organization. Nat Cell Biol. 2017; 19(12):1389-1399. DOI: 10.1038/ncb3641. View

10.

Picco A, Kukulski W, Manenschijn H, Specht T, Briggs J, Kaksonen M . The contributions of the actin machinery to endocytic membrane bending and vesicle formation. Mol Biol Cell. 2018; 29(11):1346-1358. PMC: 5994895. DOI: 10.1091/mbc.E17-11-0688. View

11.

Hurst V, Shimada K, Gasser S . Nuclear Actin and Actin-Binding Proteins in DNA Repair. Trends Cell Biol. 2019; 29(6):462-476. DOI: 10.1016/j.tcb.2019.02.010. View

12.

Du J, Fan Y, Chen T, Feng X . Lifeact and Utr230 induce distinct actin assemblies in cell nuclei. Cytoskeleton (Hoboken). 2015; 72(11):570-5. DOI: 10.1002/cm.21262. View

13.

Andrin C, McDonald D, Attwood K, Rodrigue A, Ghosh S, Mirzayans R . A requirement for polymerized actin in DNA double-strand break repair. Nucleus. 2012; 3(4):384-95. DOI: 10.4161/nucl.21055. View

14.

Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B . Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005; 24(3):473-86. PMC: 548651. DOI: 10.1038/sj.emboj.7600543. View

15.

Caridi C, Plessner M, Grosse R, Chiolo I . Nuclear actin filaments in DNA repair dynamics. Nat Cell Biol. 2019; 21(9):1068-1077. PMC: 6736642. DOI: 10.1038/s41556-019-0379-1. View

16.

Morrison A, Highland J, Krogan N, Arbel-Eden A, Greenblatt J, Haber J . INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell. 2004; 119(6):767-75. DOI: 10.1016/j.cell.2004.11.037. View

17.

Cejka P, Symington L . DNA End Resection: Mechanism and Control. Annu Rev Genet. 2021; 55:285-307. DOI: 10.1146/annurev-genet-071719-020312. View

18.

Candotti F . Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome. J Clin Immunol. 2017; 38(1):13-27. DOI: 10.1007/s10875-017-0453-z. View

19.

Lademann C, Renkawitz J, Pfander B, Jentsch S . The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination. Cell Rep. 2017; 19(7):1294-1303. DOI: 10.1016/j.celrep.2017.04.051. View

20.

Liu J, Vidi P, Lelievre S, Irudayaraj J . Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage. J Cell Sci. 2014; 128(3):599-604. PMC: 4311136. DOI: 10.1242/jcs.161885. View