The nuclear actin cytoskeleton supports DNA double-strand break repair via VCP-mediated extraction of the KU70/80 complex from damaged chromatin
- 1Institute of Molecular Biologie (IMB)
Abstract
Double-strand breaks (DSBs) are critical lesions in genomic DNA, and their accurate repair is essential for maintaining genome stability. The nuclear actin cytoskeleton has been implicated in homology-directed repair (HDR) of DSBs. However, the underlying mechanism remains poorly understood. Here, we report that Myosin VI (Myo6), an actin-based motor protein, cooperates with F-actin in end resection and DSB mobilization. Our findings reveal that Myo6 directly interacts with both KU70 and the ubiquitin-dependent segregase VCP to facilitate the extraction of the KU70/80 complex from chromatin. This process is supported by F-actin, revealing an interplay between nuclear actin dynamics and the DSB repair machinery. By elucidating the function of Myo6 and its direct interactions with key repair factors, our study provides mechanistic insight into how repair mechanisms rely on nuclear actin to safeguard genome integrity.
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BibTeX
@misc{hauschulte2026nuclear,
title = {{The nuclear actin cytoskeleton supports DNA double-strand break repair via VCP-mediated extraction of the KU70/80 complex from damaged chromatin}},
author = {K. Hauschulte and J. D. Shi and R. P. C. Wong and F. F. Stiehler and B. Ahmad and S. Richenhagen and A. Kahloon and L.-M. Vogts and M. S. Schraft and T. Strauch and S. Nick and I. Mikicic and M. Gelleri and F. Kielisch and V. Roukos and K. Rajalingam and P. Beli and A. Loewer and H. D. Ulrich and H.-P. Wollscheid},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748302},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748302v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - The nuclear actin cytoskeleton supports DNA double-strand break repair via VCP-mediated extraction of the KU70/80 complex from damaged chromatin
AU - K. Hauschulte
AU - J. D. Shi
AU - R. P. C. Wong
AU - F. F. Stiehler
AU - B. Ahmad
AU - S. Richenhagen
AU - A. Kahloon
AU - L.-M. Vogts
AU - M. S. Schraft
AU - T. Strauch
AU - S. Nick
AU - I. Mikicic
AU - M. Gelleri
AU - F. Kielisch
AU - V. Roukos
AU - K. Rajalingam
AU - P. Beli
AU - A. Loewer
AU - H. D. Ulrich
AU - H.-P. Wollscheid
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748302
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748302v1
AB - Double-strand breaks (DSBs) are critical lesions in genomic DNA, and their accurate repair is essential for maintaining genome stability. The nuclear actin cytoskeleton has been implicated in homology-directed repair (HDR) of DSBs. However, the underlying mechanism remains poorly understood. Here, we report that Myosin VI (Myo6), an actin-based motor protein, cooperates with F-actin in end resection and DSB mobilization. Our findings reveal that Myo6 directly interacts with both KU70 and the ubiquitin-dependent segregase VCP to facilitate the extraction of the KU70/80 complex from chromatin. This process is supported by F-actin, revealing an interplay between nuclear actin dynamics and the DSB repair machinery. By elucidating the function of Myo6 and its direct interactions with key repair factors, our study provides mechanistic insight into how repair mechanisms rely on nuclear actin to safeguard genome integrity.
ER -