# The novel role of microtubule regulators in the DNA damage response

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $328,332

## Abstract

DNA damage, particularly DNA double strand break (DSB), has detrimental effects on cell survival and
genomic stability. In response to DNA damage, the cell activates several evolutionarily-conserved
mechanisms to repair DNA damage, halt cell proliferation, or induce cell death. These surveillance
mechanisms, collectively defined as the DNA damage response (DDR), constitute an important etiological
factor for many human diseases, especially cancer. Moreover, the DDR is a key determinant for the
therapeutic outcome of cancer treatment using radiation and other DNA damaging agents. A long-term
goal of our laboratory is to delineate new DDR factors and mechanisms using comprehensive
experimental tools, and thereby, revealing new insights into cancer progression and treatment. In a recent
effort to systematically identify new components of the DSB “repairosome”, we identified Kif2C and several
other MT regulators as potential DSB-associated proteins. Kif2C is rapidly recruited to DNA damage sites
and plays an essential role in DSB repair. Strikingly, Kif2C mediates the spatial movement of DSBs, and
controls DNA damage-induced chromatin remodeling. These functions of Kif2C are largely dependent on
its MT depolymerase activity, and are likely to be achieved via coordination with other MT regulators. On
the other hand, DNA damage modulates Kif2C phosphorylation and MT stabilization. These findings
suggest a novel inter-organelle crosstalk between MT components and the DDR machinery that differs
from the conventional perception that MT functions exclusively as a cytoplasmic structure. These findings
also reveal new mechanistic insights into the clinical combinations of DNA damaging agents with anti-MT
poisons in cancer therapy. In this project, we will further reveal detailed mechanisms via which Kif2C
modulates the mobility of DSBs; we will uncover how Kif2C acts in concert with chromatin remodelers and
other MT regulators to govern the dynamic chromatin compaction at damage chromatin; we will
functionally characterize ATM-mediated Kif2C phosphorylation, and regulation of MT stabilization after
DNA damage. Together, the project will potentially provide paradigm shifting additions to both the DDR
and MT biology, and improve our understanding of how the cell coordinates various cellular components
and mechanisms to maintain genomic stability and cell homeostasis after DNA damage.

## Key facts

- **NIH application ID:** 10312794
- **Project number:** 5R01CA233037-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Aimin Peng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $328,332
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312794

## Citation

> US National Institutes of Health, RePORTER application 10312794, The novel role of microtubule regulators in the DNA damage response (5R01CA233037-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312794. Licensed CC0.

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