Nuclear F-actin and myosins drive relocalization of heterochromatic breaks

Abstract

Heterochromatin mainly comprises repeated DNA sequences that are prone to ectopic recombination. In Drosophila cells, 'safe' repair of heterochromatic double-strand breaks by homologous recombination relies on the relocalization of repair sites to the nuclear periphery before strand invasion. The mechanisms responsible for this movement were unknown. Here we show that relocalization occurs by directed motion along nuclear actin filaments assembled at repair sites by the Arp2/3 complex. Relocalization requires nuclear myosins associated with the heterochromatin repair complex Smc5/6 and the myosin activator Unc45, which is recruited to repair sites by Smc5/6. ARP2/3, actin nucleation and myosins also relocalize heterochromatic double-strand breaks in mouse cells. Defects in this pathway result in impaired heterochromatin repair and chromosome rearrangements. These findings identify de novo nuclear actin filaments and myosins as effectors of chromatin dynamics for heterochromatin repair and stability in multicellular eukaryotes.

β-Actin and Nuclear Myosin I are responsible for nucleolar reorganization during DNA Repair

“…Firstly identified in the cytoplasm, ACTβ and NMI are also involved in several cellular events such as cell migration, muscle contraction or organelle movements (5) and interestingly these proteins have been implicated in long-range chromosomes movements within the nucleus (6), repositioning of active genes (7) and more recently in relocalisation of double strand breaks damaged DNA from the heterochromatin compartment to the nuclear periphery in Drosophila cells (8). Intriguingly, ACTβ and NMI are also involved in RNAP1 transcription (9)(10)(11), making them the best candidates to start exploring the rDNA/RNAP1 relocalisation during DNA repair.…”

SUMO-Mediated Regulation of Nuclear Functions and Signaling Processes

“…Such targeting involves the association between sumoylated DNA repair proteins and SUMO-targeted ubiquitin ligases (STUbLs, more below) via SUMO:SIM interactions (Seeber and Gasser, 2017). Mechanisms enabling directional DNA end movement just began to emerge and involve a collaboration between nuclear actin and myosin with the Smc5/6 SUMO E3 complex (Caridi et al, 2018). …”

Keep moving and stay in a good shape to find your homologous recombination partner

“…This sustains that in human cells as well, an active mechanism that promotes DSB movement participates in homology search. The same Arp2-3 complex is also the driver of heterochromatic DSB extrusion and perinuclear relocalisation in Drosophila (Caridi et al 2018). Finally, the actin cytoskeleton seems to contribute to chromatin mobility in yeast but its requirement for DSB mobility remains to be tested (Spichal et al 2016).…”