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

Genes
Jenna M Whalen, Catherine H Freudenreich

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.

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Citations

Apr 11, 2021·Nature Cell Biology·Aline Marnef, Gaëlle Legube
Dec 7, 2020·Current Opinion in Genetics & Development·Rebecca E Brown, Catherine H Freudenreich
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Erin BonnellRaymund J Wellinger
Jun 3, 2021·International Journal of Molecular Sciences·Ya-Chu ChangAnja-Katrin Bielinsky

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Methods Mentioned

BETA
sumoylation
ChIP
fluorescence microscopy

Software Mentioned

iPOND

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