Maintaining Genome Integrity: Actin Polymerization Stabilizes Chromatin Bridges in Cytokinesis

TL;DR

This paper explains how actin polymerization helps stabilize chromatin bridges during cell division, preventing DNA damage and cancer.

Contribution

The study reveals a new mechanism involving the Sun1/2-Nesprin-2-LINC complex and PDZ RhoGEF signaling in actin patch formation during cytokinesis.

Findings

The Sun1/2-Nesprin-2-LINC complex generates mechanical tension on daughter nuclei with chromatin bridges.

PDZ RhoGEF activates RhoA signaling pathways to promote actin patches and stabilize chromatin bridges.

Actin patches prevent chromatin bridge breakage during cytokinesis.

Abstract

In mitotic cell division, cytokinesis is followed by abscission, the final separation of the cytoplasmic canal, to release the two genetically identical daughter cells; however, sometimes chromatin bridges connecting the daughter nuclei appear. Preserving intact chromatin bridges is crucial because their breakage can cause DNA damage, aneuploidy, and cancer predisposition. For this purpose, cells use two main mechanisms: first, they activate the abscission checkpoint, a mechanism that delays the final cut of the cytoplasmic canal to prevent chromatin bridge breakage and secondly, they form accumulations of actin (“actin patches”) at the base of the intercellular canal to stabilize chromatin bridges. Here, we highlight new findings from our laboratory on how human cells “sense” chromatin bridges and remodel the actin cytoskeleton to generate actin patches in cytokinesis. More specifically, we discuss findings showing that the nuclear membrane Sun1/2-Nesprin-2-LINC (linker of nucleoskeleton and cytoskeleton) complex promotes the generation of mechanical tension on daughter nuclei with chromatin bridges. This tension leads to accumulation of Sun1/2 and Nesprin-2, and cytoplasmic accumulation of PDZ RhoGEF (PDZ domain-containing Rho guanine nucleotide exchange factor) at the base of the intercellular canal. In turn, PDZ RhoGEF activates downstream RhoA-ROCK-LIMK-Cofilin and RhoA-mDia1 signaling pathways to promote actin patches and prevent chromatin bridge breakage in cytokinesis.

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