Location, Location, Location: The Role of Nuclear Positioning in the Repair of Collapsed Forks and Protection of Genome Stability

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2020 Jun 13

PMID 32526925

Citations 11

Authors

Jenna M Whalen

Catherine H Freudenreich

Affiliations

Soon will be listed here.

Abstract

Components of the nuclear pore complex (NPC) have been shown to play a crucial role in protecting against replication stress, and recovery from some types of stalled or collapsed replication forks requires movement of the DNA to the NPC in order to maintain genome stability. The role that nuclear positioning has on DNA repair has been investigated in several systems that inhibit normal replication. These include structure forming sequences (expanded CAG repeats), protein mediated stalls (replication fork barriers (RFBs)), stalls within the telomere sequence, and the use of drugs known to stall or collapse replication forks (HU + MMS or aphidicolin). Recently, the mechanism of relocation for collapsed replication forks to the NPC has been elucidated. Here, we will review the types of replication stress that relocate to the NPC, the current models for the mechanism of relocation, and the currently known protective effects of this movement.

Citing Articles

The fission yeast SUMO-targeted ubiquitin ligase Slx8 functionally associates with clustered centromeres and the silent mating-type region at the nuclear periphery.

Chakraborty S, Strachan J, Schirmeisen K, Besse L, Mercier E, Freon K Biol Open. 2025; 13(12.

PMID: 39786922 PMC: 11708773. DOI: 10.1242/bio.061746.

STIM1 translocation to the nucleus protects cells from DNA damage.

Sanchez-Lopez I, Orantos-Aguilera Y, Pozo-Guisado E, Alvarez-Barrientos A, Lilla S, Zanivan S Nucleic Acids Res. 2024; 52(5):2389-2415.

PMID: 38224453 PMC: 10954485. DOI: 10.1093/nar/gkae001.

Nuclear pore complexes mediate subtelomeric gene silencing by regulating PCNA levels on chromatin.

Choudhry S, Neal M, Li S, Navare A, van Eeuwen T, Wozniak R J Cell Biol. 2023; 222(9).

PMID: 37358474 PMC: 10292210. DOI: 10.1083/jcb.202207060.

Determinants of RPA megafoci localization to the nuclear periphery in response to replication stress.

Kim S, Forsburg S G3 (Bethesda). 2022; 12(7).

PMID: 35567482 PMC: 9258583. DOI: 10.1093/g3journal/jkac116.

Nuclear Lipid Droplet Birth during Replicative Stress.

Kumanski S, Forey R, Cazevieille C, Moriel-Carretero M Cells. 2022; 11(9).

PMID: 35563696 PMC: 9105094. DOI: 10.3390/cells11091390.

References

Whalen J, Dhingra N, Wei L, Zhao X, Freudenreich C . Relocation of Collapsed Forks to the Nuclear Pore Complex Depends on Sumoylation of DNA Repair Proteins and Permits Rad51 Association. Cell Rep. 2020; 31(6):107635. PMC: 7344339. DOI: 10.1016/j.celrep.2020.107635. View

Cobb J, Schleker T, Rojas V, Bjergbaek L, Tercero J, Gasser S . Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations. Genes Dev. 2005; 19(24):3055-69. PMC: 1315408. DOI: 10.1101/gad.361805. View

Bylebyl G, Belichenko I, Johnson E . The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. J Biol Chem. 2003; 278(45):44113-20. DOI: 10.1074/jbc.M308357200. View

Horigome C, Oma Y, Konishi T, Schmid R, Marcomini I, Hauer M . SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Mol Cell. 2014; 55(4):626-39. DOI: 10.1016/j.molcel.2014.06.027. View

Edwards D, Machwe A, Wang Z, Orren D . Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by replicative and translesion polymerases, revealing their potential to lead to genetic change. PLoS One. 2014; 9(1):e80664. PMC: 3891601. DOI: 10.1371/journal.pone.0080664. View

Oshidari R, Strecker J, Chung D, Abraham K, Chan J, Damaren C . Nuclear microtubule filaments mediate non-linear directional motion of chromatin and promote DNA repair. Nat Commun. 2018; 9(1):2567. PMC: 6028458. DOI: 10.1038/s41467-018-05009-7. View

Bologna S, Altmannova V, Valtorta E, Koenig C, Liberali P, Gentili C . Sumoylation regulates EXO1 stability and processing of DNA damage. Cell Cycle. 2015; 14(15):2439-50. PMC: 4615030. DOI: 10.1080/15384101.2015.1060381. View

Loeillet S, Palancade B, Cartron M, Thierry A, Richard G, Dujon B . Genetic network interactions among replication, repair and nuclear pore deficiencies in yeast. DNA Repair (Amst). 2005; 4(4):459-68. DOI: 10.1016/j.dnarep.2004.11.010. View

Aguilera P, Whalen J, Minguet C, Churikov D, Freudenreich C, Simon M . The nuclear pore complex prevents sister chromatid recombination during replicative senescence. Nat Commun. 2020; 11(1):160. PMC: 6952416. DOI: 10.1038/s41467-019-13979-5. View

10.

Hochstrasser M . SP-RING for SUMO: new functions bloom for a ubiquitin-like protein. Cell. 2001; 107(1):5-8. DOI: 10.1016/s0092-8674(01)00519-0. View

11.

Jay K, Smith D, Blackburn E . Early Loss of Telomerase Action in Yeast Creates a Dependence on the DNA Damage Response Adaptor Proteins. Mol Cell Biol. 2016; 36(14):1908-19. PMC: 4936065. DOI: 10.1128/MCB.00943-15. View

12.

Ohki R, Ishikawa F . Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats. Nucleic Acids Res. 2004; 32(5):1627-37. PMC: 390322. DOI: 10.1093/nar/gkh309. View

13.

Woodward A, Gohler T, Luciani M, Oehlmann M, Ge X, Gartner A . Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006; 173(5):673-83. PMC: 2063885. DOI: 10.1083/jcb.200602108. View

14.

Golebiowski F, Matic I, Tatham M, Cole C, Yin Y, Nakamura A . System-wide changes to SUMO modifications in response to heat shock. Sci Signal. 2009; 2(72):ra24. DOI: 10.1126/scisignal.2000282. View

15.

Saponaro M, Callahan D, Zheng X, Krejci L, Haber J, Klein H . Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair. PLoS Genet. 2010; 6(2):e1000858. PMC: 2829061. DOI: 10.1371/journal.pgen.1000858. View

16.

Lisby M, Geli V . DNA damage response to eroded telomeres. Cell Cycle. 2009; 8(22):3617-8. DOI: 10.4161/cc.8.22.9945. View

17.

Sacher M, Pfander B, Hoege C, Jentsch S . Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat Cell Biol. 2006; 8(11):1284-90. DOI: 10.1038/ncb1488. View

18.

Branzei D, Sollier J, Liberi G, Zhao X, Maeda D, Seki M . Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell. 2006; 127(3):509-22. DOI: 10.1016/j.cell.2006.08.050. View

19.

Oza P, Jaspersen S, Miele A, Dekker J, Peterson C . Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 2009; 23(8):912-27. PMC: 2675867. DOI: 10.1101/gad.1782209. View

20.

Zhao X, Wu C, Blobel G . Mlp-dependent anchorage and stabilization of a desumoylating enzyme is required to prevent clonal lethality. J Cell Biol. 2004; 167(4):605-11. PMC: 2172573. DOI: 10.1083/jcb.200405168. View