Cited by 239DNA Repair MechanismsDNA and Nucleic Acid ChemistryBacterial Genetics and Biotechnology

Mre11 Protein Complex Prevents Double-Strand Break Accumulation during Chromosomal DNA Replication

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Costanzo, Vincenzo, Robertson, Kirsten, Bibikova, Marina, Kim, Edward, Grieco, Domenico, Gottesman, Max, Carroll, Dana, Gautier, Jean·2001·Molecular Cell

Abstract

Mre11 complex promotes repair of DNA double-strand breaks (DSBs). Xenopus Mre11 (X-Mre11) has been cloned, and its role in DNA replication and DNA damage checkpoint studied in cell-free extracts. DSBs stimulate the phosphorylation and 3'-5' exonuclease activity of X-Mre11 complex. This induced phosphorylation is ATM independent. Phosphorylated X-Mre11 is found associated with replicating nuclei. X-Mre11 complex is required to yield normal DNA replication products. Genomic DNA replicated in extracts immunodepleted of X-Mre11 complex accumulates DSBs as demonstrated by TUNEL assay and reactivity to phosphorylated histone H2AX antibodies. In contrast, the ATM-dependent DNA damage checkpoint that blocks DNA replication initiation is X-Mre11 independent. These results strongly suggest that the function of X-Mre11 complex is to repair DSBs that arise during normal DNA replication, thus unraveling a critical link between recombination-dependent repair and DNA replication.

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Authors
Costanzo, V., Robertson, K., Bibikova, M., Kim, E., Grieco, D., Gottesman, M., Carroll, D., & Gautier, J.
Affiliations
  • Columbia University (US)
  • University of Utah (US)
  • University of Naples Federico II (IT)
Corresponding author
Gautier, Jean
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2001-07
Volume
8
Issue
1
Pages
137-147
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2099518892
Cited by
239
References
53
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 10 · 2015: 6 · 2014: 9 · 2013: 14 · 2012: 9
FWCI
7.93
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
  • Zenodo (CERN European Organization for Nuclear Research) (other-oa)
Funders
  • National Institutes of Health (5r01gm056781-04)
  • National Institute of General Medical Sciences (R01 GM56781)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Mre11 complex, DNA double-strand break repair, DNA replication, DNA damage checkpoint, 3'-5' exonuclease activity, H2AX phosphorylation, Xenopus, cell-free extracts
MeSH terms
MRE11 Homologue Protein, Amino Acid Sequence, Animals, Antifungal Agents, Caffeine, Cell Cycle, Cell Nucleus, Cell-Free System, Chromatin, DNA Damage, DNA Repair, DNA Replication, DNA-Binding Proteins, Humans, Models, Biological, Molecular Sequence Data, Oocytes, Phosphodiesterase Inhibitors, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Pyrans, Recombinant Proteins, Spiro Compounds, Xenopus laevis, Immunoblotting, In Situ Nick-End Labeling

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