Microtubule-associated proteins MAP7 and MAP7D1 promote DNA double-strand break repair in the G1 cell cycle phase
Open accessPublished version of a preprint
Abstract
The DNA-damage response is a complex signaling network that guards genomic integrity. The microtubule cytoskeleton is involved in the repair of DNA double-strand breaks; however, little is known about which cytoskeleton-related proteins are involved in DNA repair and how. Using quantitative proteomics, we discovered that microtubule associated proteins MAP7 and MAP7D1 interact with several DNA repair proteins including DNA double-strand break repair proteins RAD50, BRCA1 and 53BP1. We observed that downregulation of MAP7 and MAP7D1 leads to increased phosphorylation of p53 after γ-irradiation. Moreover, we determined that the downregulation of MAP7D1 leads to a strong G1 arrest and that the downregulation of MAP7 and MAP7D1 in G1 arrested cells negatively affects DNA repair, recruitment of RAD50 to chromatin and localization of 53BP1 to the sites of damage. These findings describe for the first time a novel function of MAP7 and MAP7D1 in cell cycle regulation and repair of DNA double-strand breaks.
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Cites
The central role of DNA damage in the ageing process
Schumacher, B., Pothof, J., Vijg, J., & Hoeijmakers, J. H. J. (2021) · Nature · doi:10.1038/s41586-021-03307-7 · Cited by 907 · see citing works
Nuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · see citing works
Lamin B1 sequesters 53BP1 to control its recruitment to DNA damage
Etourneaud, L., Moussa, A., Rass, E., Genet, D., Willaume, S., Chabance-Okumura, C., Wanschoor, P., Picotto, J., Thézé, B., Dépagne, J., et al. (2021) · Science Advances · doi:10.1126/sciadv.abb3799 · Cited by 54 · see citing works
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- Authors
- Dullovi, A., Ozgencil, M., Rajvee, V., Tse, W. Y., Cutillas, P. R., Martin, S. A., & Hořejší, Z.
- Affiliations
- Queen Mary University of London (GB)
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2023-03
- Volume
- 26
- Issue
- 3
- Pages
- 106107
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9958362
- OpenAlex
- W4318773798
- Cited by
- 15
- References
- 3
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 2
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (200462/Z/16/Z)
- Queen Mary University of London
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- MAP7, microtubule-associated proteins, DNA double-strand break repair, G1 cell cycle arrest, DNA damage response, RAD50, BRCA1, 53BP1, p53 phosphorylation, gamma irradiation, microtubule cytoskeleton, chromatin recruitment
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