# PICH impacts the spindle assembly checkpoint via its DNA translocase and SUMO-interaction activities

## TL;DR

This study shows how PICH, a chromatin remodeling enzyme, influences the spindle assembly checkpoint by affecting Bub1 at kinetochores through SUMOylation.

## Contribution

The paper reveals a novel role of PICH in modulating the spindle assembly checkpoint via SUMOylation and DNA translocase activities.

## Key findings

- PICH regulates the spindle assembly checkpoint by modulating Bub1 association at kinetochores.
- Loss of PICH remodeling or SUMO-interaction functions causes mitotic defects and SAC activation.
- Proteomics analysis identified Bub1 as a candidate affected by PICH activity.

## Abstract

Genome-edited cell lines for PICH depletion or replacement to loss of function mutants revealed an unidentified PICH function impacting SAC activity through modulating Bub1 association at kinetochores.

Either inhibiting or stabilizing SUMOylation in mitosis causes defects in chromosome segregation, suggesting that dynamic mitotic SUMOylation of proteins is critical to maintain integrity of the genome. Polo-like kinase 1–interacting checkpoint helicase (PICH), a mitotic chromatin remodeling enzyme, interacts with SUMOylated chromosomal proteins via three SUMO-interacting motifs (SIMs) to control their association with chromosomes. Using cell lines with conditional PICH depletion/PICH replacement, we revealed mitotic defects associated with compromised PICH functions toward SUMOylated chromosomal proteins. Defects in either remodeling activity or SIMs of PICH delayed mitotic progression caused by activation of the spindle assembly checkpoint (SAC) indicated by extended duration of Mad1 foci at centromeres. Proteomics analysis of chromosomal SUMOylated proteins whose abundance is controlled by PICH activity identified candidate proteins to explain the SAC activation phenotype. Among the identified candidates, Bub1 kinetochore abundance is increased upon loss of PICH. Our results demonstrated a novel relationship between PICH and the SAC, where PICH directly or indirectly affects Bub1 association at the kinetochore and impacts SAC activity to control mitosis.