Lamin B1 Acetylation Slows the G1 to S Cell Cycle Transition Through Inhibition of DNA Repair

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2021 Feb 3

PMID 33533922

Citations 14

Authors

Laura A Murray-Nerger

Joshua L Justice

Pranav Rekapalli

Josiah E Hutton

Ileana M Cristea

Affiliations

Soon will be listed here.

Abstract

The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.

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References

Davison A, Eberle R, Ehlers B, Hayward G, McGeoch D, Minson A . The order Herpesvirales. Arch Virol. 2008; 154(1):171-7. PMC: 3552636. DOI: 10.1007/s00705-008-0278-4. View

Simon D, Wilson K . Partners and post-translational modifications of nuclear lamins. Chromosoma. 2013; 122(1-2):13-31. PMC: 3619935. DOI: 10.1007/s00412-013-0399-8. View

Branon T, Bosch J, Sanchez A, Udeshi N, Svinkina T, Carr S . Efficient proximity labeling in living cells and organisms with TurboID. Nat Biotechnol. 2018; 36(9):880-887. PMC: 6126969. DOI: 10.1038/nbt.4201. View

Buchkovich N, Maguire T, Alwine J . Role of the endoplasmic reticulum chaperone BiP, SUN domain proteins, and dynein in altering nuclear morphology during human cytomegalovirus infection. J Virol. 2010; 84(14):7005-17. PMC: 2898220. DOI: 10.1128/JVI.00719-10. View

Bennardo N, Cheng A, Huang N, Stark J . Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet. 2008; 4(6):e1000110. PMC: 2430616. DOI: 10.1371/journal.pgen.1000110. View

Choudhary C, Weinert B, Nishida Y, Verdin E, Mann M . The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol. 2014; 15(8):536-50. DOI: 10.1038/nrm3841. View

Lemaitre C, Grabarz A, Tsouroula K, Andronov L, Furst A, Pankotai T . Nuclear position dictates DNA repair pathway choice. Genes Dev. 2014; 28(22):2450-63. PMC: 4233239. DOI: 10.1101/gad.248369.114. View

Peter M, Nakagawa J, Doree M, Labbe J, Nigg E . In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell. 1990; 61(4):591-602. DOI: 10.1016/0092-8674(90)90471-p. View

Mehta A, Haber J . Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harb Perspect Biol. 2014; 6(9):a016428. PMC: 4142968. DOI: 10.1101/cshperspect.a016428. View

10.

Pascual-Reguant L, Blanco E, Galan S, Le Dily F, Cuartero Y, Serra-Bardenys G . Lamin B1 mapping reveals the existence of dynamic and functional euchromatin lamin B1 domains. Nat Commun. 2018; 9(1):3420. PMC: 6109041. DOI: 10.1038/s41467-018-05912-z. View

11.

Murray L, Sheng X, Cristea I . Orchestration of protein acetylation as a toggle for cellular defense and virus replication. Nat Commun. 2018; 9(1):4967. PMC: 6251895. DOI: 10.1038/s41467-018-07179-w. View

12.

Acs K, Luijsterburg M, Ackermann L, Salomons F, Hoppe T, Dantuma N . The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks. Nat Struct Mol Biol. 2011; 18(12):1345-50. DOI: 10.1038/nsmb.2188. View

13.

Rothkamm K, Kruger I, Thompson L, Lobrich M . Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol. 2003; 23(16):5706-15. PMC: 166351. DOI: 10.1128/MCB.23.16.5706-5715.2003. View

14.

Fontana G, Hess D, Reinert J, Mattarocci S, Falquet B, Klein D . Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane. Nat Commun. 2019; 10(1):2535. PMC: 6557901. DOI: 10.1038/s41467-019-10349-z. View

15.

Butin-Israeli V, Adam S, Jain N, Otte G, Neems D, Wiesmuller L . Role of lamin b1 in chromatin instability. Mol Cell Biol. 2014; 35(5):884-98. PMC: 4323489. DOI: 10.1128/MCB.01145-14. View

16.

Gesson K, Rescheneder P, Skoruppa M, von Haeseler A, Dechat T, Foisner R . A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha. Genome Res. 2016; 26(4):462-73. PMC: 4817770. DOI: 10.1101/gr.196220.115. View

17.

Ward I, Minn K, van Deursen J, Chen J . p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol Cell Biol. 2003; 23(7):2556-63. PMC: 150747. DOI: 10.1128/MCB.23.7.2556-2563.2003. View

18.

Jung H, Nobumori C, Goulbourne C, Tu Y, Lee J, Tatar A . Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration. Proc Natl Acad Sci U S A. 2013; 110(21):E1923-32. PMC: 3666708. DOI: 10.1073/pnas.1303916110. View

19.

Freeman Jr R . The 'indirect' effects of cytomegalovirus infection. Am J Transplant. 2009; 9(11):2453-8. DOI: 10.1111/j.1600-6143.2009.02824.x. View

20.

Liu N, Sun J, Kono K, Horikoshi Y, Ikura T, Tong X . Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage. FASEB J. 2015; 29(6):2514-25. DOI: 10.1096/fj.14-265546. View