hMre11 and hRad50 Nuclear Foci Are Induced During the Normal Cellular Response to DNA Double-Strand Breaks †
Open accessAbstract
We previously identified a conserved multiprotein complex that includes hMre11 and hRad50. In this study, we used immunofluorescence to investigate the role of this complex in DNA double-strand break (DSB) repair. hMre11 and hRad50 form discrete nuclear foci in response to treatment with DSB-inducing agents but not in response to UV irradiation. hMre11 and hRad50 foci colocalize after treatment with ionizing radiation and are distinct from those of the DSB repair protein, hRad51. Our data indicate that an irradiated cell is competent to form either hMre11-hRad50 foci or hRad51 foci, but not both. The multiplicity of hMre11 and hRad50 foci is much higher in the DSB repair-deficient cell line 180BR than in repair-proficient cells. hMre11-hRad50 focus formation is markedly reduced in cells derived from ataxia-telangiectasia patients, whereas hRad51 focus formation is markedly increased. These experiments support genetic evidence from Saccharomyces cerevisiae indicating that Mre11-Rad50 have roles distinct from that of Rad51 in DSB repair. Further, these data indicate that hMre11-hRad50 foci form in response to DNA DSBs and are dependent upon a DNA damage-induced signaling pathway.
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Eight hours after DNA damage, a portion of cells contain prominent Mre11/Rad50/Nbs1 foci, and these foci are thought to be sites of remaining DNA damage.
“Previous studies have demonstrated that 8 h after DNA damage, a portion of cells contain prominent Mre11/Rad50/Nbs1 foci, and these foci are thought to be sites of remaining DNA damage (8, 30).”
From Mdm2 Promotes Genetic Instability and Transformation Independent of p53 (2008) · cites this paper as [30]
The Results (page not available) report that more than 60% of irradiated cells had hMre11 and hRad50 foci at 8 hours. The paper does not establish Nbs1 as part of those foci, and its Conclusion (page not available) says that locating the foci at DNA break sites awaits further study. Thus, it supports the timing and presence of foci, but not the full claim about their composition and location at remaining damage. (LLM, conf=0.88)
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A DNA Damage Response Pathway Controlled by Tel1 and the Mre11 Complex
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Self-citationDNA Damage-Dependent Nuclear Dynamics of the Mre11 Complex
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Self-citationPhosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage
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The cellular response to DNA double-strand breaks: defining the sensors and mediators
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Self-citationChk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair
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The controlling role of ATM in homologous recombinational repair of DNA damage
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Nuclear Retention of ATM at Sites of DNA Double Strand Breaks
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Cancer predisposition and hematopoietic failure in <i> Rad50 <sup>S/S</sup> </i> mice
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The mismatch repair system is required for S-phase checkpoint activation
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Chk2 Activation Dependence on Nbs1 after DNA Damage
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The Mre11/Rad50/Nbs1 complex limits adeno-associated virus transduction and replication
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- Authors
- Maser, R. S., Monsen, K. J., Nelms, B. E., & Petrini, J. H. J.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Wisconsin System (US)
- Corresponding author
- Petrini, John H. J.
- ORCID
- Petrini, John H. J.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1997-10
- Volume
- 17
- Issue
- 10
- Pages
- 6087-6096
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC232458
- OpenAlex
- W2131646714
- Cited by
- 499
- References
- 81
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 11 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 12 · 2014: 9 · 2013: 12 · 2012: 14
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Cancer Society
- March of Dimes Foundation
- University of Wisconsin-Madison
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008349, T32GM007133)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Mre11-Rad50 complex, DNA double-strand break repair, nuclear foci, RAD51, ataxia telangiectasia, ionizing radiation, UV irradiation, DNA damage signaling
- MeSH terms
- Ataxia Telangiectasia, Cell Nucleus, Cells, Cultured, DNA Damage, DNA Repair, DNA-Binding Proteins, Endodeoxyribonucleases, Enzyme Inhibitors, Etoposide, Exodeoxyribonucleases, Fibroblasts, Fungal Proteins, Gamma Rays, Humans, Mutation, Proteins, Signal Transduction, G2 Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Saccharomyces cerevisiae Proteins, Rad51 Recombinase, Topoisomerase II Inhibitors, Ataxia Telangiectasia Mutated Proteins
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