# Timing Control of Centromeric Cohesion through Centromere-localized Sgo1

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $319,200

## Abstract

Project Summary
Protection and subsequent de-protection of centromeric cohesion during mitosis is essential for
preventing chromosome missegregation and preserving genomic stability. This timing control of
centromeric cohesion is defined by the inner-centromeric (the place between two sister centromeres)
installment and removal of Shugoshin (Sgo1) proteins, but the underlying mechanisms that control the
Sgo1 localization at inner centromeres are little known. The long-term goal is to understand the molecular
mechanisms of chromosome segregation and their relationships with aneuploidy-driven processes and
diseases. The objective of this proposal is to determine the essential mechanisms controlling the
inner-centromere localization of Sgo1. We previously found that Bub1-dependent RNA polymerase II
transcription is involved in installing Sgo1 at inner centromeres after initial kinetochore recruitment. Our
preliminary data show that SET, a cellular PP2A inhibitor, can directly bind Sgo1 and inhibit the
Sgo1-cohesin interaction. The central hypothesis is that Bub1-dependent actively-transcribing RNAP
(RNA polymerase) II binds and delivers Sgo1 to inner centromeres at early mitosis, and that SET and/or
PP1 (phosphatase 1) removes Sgo1 from inner centromeres at metaphase-to-anaphase transition. The
rationale underlying this research is that the exploration of the regulation of centromeric cohesion is
critical to understand its role in genome stability. Guided by strong preliminary data, this hypothesis will be
tested by pursuing two specific aims: 1) Determine the function and regulation of centromeric transcription
in mitosis; and 2) Determine how centromeric cohesion is de-protected. Under the first aim, we will
determine if Bub1-H2A-pT120 maintains the transcription-promoting epigenetic histone marks to facilitate
transcription, and if elongating RNAP II binds and delivers Sgo1 to centromeric cohesin, thus enabling
Sgo1 function. Under the second aim, we will determine if SET and/or PP1 removes Sgo1 from inner
centromeres at metaphase-to-anaphase transition by disrupting the Sgo1-cohein interaction. The
proposed research is innovative, in the application’s opinion, because it departs the status quo by
revealing totally novel and important mechanisms that determine the timing control of centromeric
cohesion. This research is also significant, because it is expected to vertically advance and expand
understanding of the molecular mechanisms that are essential for proper chromosome segregation and
prevent aneuploidy. Ultimately, such knowledge will help identify potential targets for future development
of new anti-cancer therapy.

## Key facts

- **NIH application ID:** 10249286
- **Project number:** 5R01GM124018-04
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Hong Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,200
- **Award type:** 5
- **Project period:** 2018-09-10 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249286

## Citation

> US National Institutes of Health, RePORTER application 10249286, Timing Control of Centromeric Cohesion through Centromere-localized Sgo1 (5R01GM124018-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10249286. Licensed CC0.

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