# Regulation of cell cycle transitions by cyclin-dependent kinase in trypanosomes

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $467,406

## Abstract

Project Summary
 A central question in the study of cell cycle regulation is, how the cell cycle transitions are controlled to
allow the transition to the next cell cycle stage at a right time? Such control mechanisms are critical for
maintaining genome integrity because premature transition from one stage to the next stage of the cell cycle
can lead to aneuploidy and, hence, cell death. Four major cell cycle transition points, the G1/S transition, the
G2/M transition, the metaphase/anaphase transition, and the mitosis/cytokinesis transition, are under stringent
control, but how they are regulated at the molecular level in T. brucei, a protozoan parasite and the causative
agent of human sleeping sickness, remains poorly understood. Cyclin-dependent kinases (CDKs) are key
regulators of the cell cycle transitions in eukaryotes, and T. brucei employs the CDK-related kinase CRK1 to
control the G1/S transition, CRK2 to promote S-phase progression, and CRK3 to govern the G2/M transition.
The roles of CRK1 in controlling the nuclear events in promoting the G1/S transition and the role of CRK2 in
regulating S-phase progression have been recently revealed by us. However, the molecular mechanisms
underlying the G2/M transition and the metaphase/anaphase transition are still elusive. Further, it is generally
accepted that T. brucei lacks several cell cycle checkpoints, including the spindle assembly checkpoint, and it
is unclear how T. brucei recognizes the genomic errors occurred during the cell cycle and prevents erroneous
genome duplication and premature genome segregation. Our recent discovery of a novel DNA damage-
induced metaphase checkpoint suggests a kinetochore-based checkpoint machinery in T. brucei, but the
underlying mechanism remains largely unknown. The current proposal aims to understand the control of the
G2/M transition by CRK3-mediated regulation of the chromosomal passenger complex, the control of
metaphase/anaphase transition by CRK3-mediated regulation of kinetochore proteins, and the mechanism of
the metaphase checkpoint mediated by KKIP5 and its associated proteins. The outcomes from these
investigations not only will have important biological significance, but also could provide novel targets for anti-
trypanosomiasis chemotherapy.

## Key facts

- **NIH application ID:** 10362149
- **Project number:** 2R01AI118736-06A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Ziyin Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $467,406
- **Award type:** 2
- **Project period:** 2016-05-13 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10362149

## Citation

> US National Institutes of Health, RePORTER application 10362149, Regulation of cell cycle transitions by cyclin-dependent kinase in trypanosomes (2R01AI118736-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10362149. Licensed CC0.

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