SUMO-Based Regulation of Nuclear Positioning to Spatially Regulate Homologous Recombination Activities at Replication Stress Sites

DNA lesions have properties that allow them to escape their nuclear compartment to achieve DNA repair in another one. Recent studies uncovered that the replication fork, when its progression is impaired, exhibits increased mobility when changing nuclear positioning and anchors to nuclear pore complexes, where specific types of homologous recombination pathways take place. In yeast models, increasing evidence points out that nuclear positioning is regulated by small ubiquitin-like modifier (SUMO) metabolism, which is pivotal to maintaining genome integrity at sites of replication stress. Here, we review how SUMO-based pathways are instrumental to spatially segregate the subsequent steps of homologous recombination during replication fork restart. In particular, we discussed how routing towards nuclear pore complex anchorage allows distinct homologous recombination pathways to take place at halted replication forks.

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The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal

Nature Communications ◽

10.1038/s41467-020-19516-z ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Karol Kramarz ◽

Kamila Schirmeisen ◽

Virginie Boucherit ◽

Anissia Ait Saada ◽

Claire Lovo ◽

...

Keyword(s):

Dna Synthesis ◽

Replication Fork ◽

Inhibitory Effect ◽

Dna Lesions ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Spatial Control ◽

Sumo Protease ◽

Sumo Ligase ◽

Pore Complexes

Abstract Nuclear Pore complexes (NPCs) act as docking sites to anchor particular DNA lesions facilitating DNA repair by elusive mechanisms. Using replication fork barriers in fission yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzymatic activity. The E3 SUMO ligase Pli1 acts at arrested forks to safeguard integrity of nascent strands and generates poly-SUMOylation which promote relocation to NPCs but impede the resumption of DNA synthesis by homologous recombination (HR). Anchorage to NPCs allows SUMO removal by the SENP SUMO protease Ulp1 and the proteasome, promoting timely resumption of DNA synthesis. Preventing Pli1-mediated SUMO chains was sufficient to bypass the need for anchorage to NPCs and the inhibitory effect of poly-SUMOylation on HR-mediated DNA synthesis. Our work establishes a novel spatial control of Recombination-Dependent Replication (RDR) at a unique sequence that is distinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences.

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Faculty Opinions recommendation of Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3113958.2797056 ◽

2010 ◽

Author(s):

Jonathan Bogan

Keyword(s):

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Nuclear Positioning ◽

Mitotic Entry ◽

Pore Complexes

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Bicaudal D2, Dynein, and Kinesin-1 Associate with Nuclear Pore Complexes and Regulate Centrosome and Nuclear Positioning during Mitotic Entry

PLoS Biology ◽

10.1371/journal.pbio.1000350 ◽

2010 ◽

Vol 8 (4) ◽

pp. e1000350 ◽

Cited By ~ 190

Author(s):

Daniël Splinter ◽

Marvin E. Tanenbaum ◽

Arne Lindqvist ◽

Dick Jaarsma ◽

Annette Flotho ◽

...

Keyword(s):

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Nuclear Positioning ◽

Mitotic Entry ◽

Pore Complexes

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

Genes ◽

10.3390/genes11060635 ◽

2020 ◽

Vol 11 (6) ◽

pp. 635

Author(s):

Jenna M. Whalen ◽

Catherine H. Freudenreich

Keyword(s):

Genome Stability ◽

Replication Stress ◽

Cag Repeats ◽

Nuclear Pore ◽

Replication Forks ◽

Protective Effects ◽

Nuclear Positioning ◽

Telomere Sequence ◽

Maintain Genome Stability

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.

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Nuclear Envelope Dynamics During Mitosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100103188 ◽

1988 ◽

Vol 46 ◽

pp. 224-225

Author(s):

Brian Burke

Keyword(s):

Nuclear Envelope ◽

Membrane Vesicles ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Animal Cells ◽

Interphase Chromosome ◽

Lamin B ◽

Chromosome Architecture ◽

Complex Membrane ◽

Pore Complexes

The nuclear envelope is a complex membrane structure that forms the boundary of the nuclear compartment in eukaryotes. It regulates the passage of macromolecules between the two compartments and may be important for organizing interphase chromosome architecture. In interphase animal cells it forms a remarkably stable structure consisting of a double membrane ouerlying a protein meshwork or lamina and penetrated by nuclear pore complexes. The latter form the channels for nucleocytoplasmic exchange of macromolecules, At the onset of mitosis, however, it rapidly disassembles, the membranes fragment to yield small vesicles and the lamina, which is composed of predominantly three polypeptides, lamins R, B and C (MW approx. 74, 68 and 65 kDa respectiuely), breaks down. Lamins B and C are dispersed as monomers throughout the mitotic cytoplasm, while lamin B remains associated with the nuclear membrane vesicles.

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