Association of DNA Polymerase μ (pol μ) with Ku and Ligase IV: Role for pol μ in End-Joining Double-Strand Break Repair
Open accessAbstract
Mammalian DNA polymerase mu (pol mu) is related to terminal deoxynucleotidyl transferase, but its biological role is not yet clear. We show here that after exposure of cells to ionizing radiation (IR), levels of pol mu protein increase. pol mu also forms discrete nuclear foci after IR, and these foci are largely coincident with IR-induced foci of gammaH2AX, a previously characterized marker of sites of DNA double-strand breaks. pol mu is thus part of the cellular response to DNA double-strand breaks. pol mu also associates in cell extracts with the nonhomologous end-joining repair factor Ku and requires both Ku and another end-joining factor, XRCC4-ligase IV, to form a stable complex on DNA in vitro. pol mu in turn facilitates both stable recruitment of XRCC4-ligase IV to Ku-bound DNA and ligase IV-dependent end joining. In contrast, the related mammalian DNA polymerase beta does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol mu in facilitating joining mediated by these factors. Our data thus support an important role for pol mu in the end-joining pathway for repair of double-strand breaks.
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The NHEJ process is regulated by protein-protein interactions such as Ku/Ligase IV-XRCC4/polymerase μ.
“This entire process is regulated by protein-protein interactions such as the one formed by Ku/Ligase IV-XRCC4/polymerase μ [65].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [65]
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- Authors
- Mahajan, K. N., Nick McElhinny, S. A., Mitchell, B. S., & Ramsden, D. A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Lineberger Comprehensive Cancer Center
- UNC Lineberger Comprehensive Cancer Center (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2002-07-01
- Volume
- 22
- Issue
- 14
- Pages
- 5194-5202
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC139779
- OpenAlex
- W2100518470
- Cited by
- 293
- References
- 38
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 12 · 2016: 4 · 2015: 6 · 2014: 13 · 2013: 10 · 2012: 20
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01-CA34085, U01CA097096, R01CA084442, R01 CA 84442-01, R01CA034085)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- DNA polymerase mu, Ku protein, ligase IV, XRCC4, non-homologous end joining, DNA double-strand break repair, ionizing radiation, γH2AX foci, DNA polymerase beta, terminal deoxynucleotidyl transferase, DNA repair foci
- MeSH terms
- Ku Autoantigen, Cell Line, DNA Damage, DNA-Directed DNA Polymerase, DNA Repair, DNA Helicases, DNA-Binding Proteins, Humans, Nuclear Proteins, Recombinant Fusion Proteins, DNA Polymerase beta, Antigens, Nuclear, In Vitro Techniques
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