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Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay
Published on: August 23, 2024
Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand
J-B Bae1, S S Mukhopadhyay, L Liu
1Department of Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oncogene
|May 13, 2008
Summary
Snm1B/Apollo is crucial for DNA repair, specifically activating the ATM checkpoint after DNA interstrand cross-link damage. Its deficiency leads to sensitivity to cross-linking agents and impaired S-phase checkpoint control.
Area of Science:
- DNA repair mechanisms
- Cellular response to DNA damage
- Molecular biology
Background:
- DNA interstrand cross-links (ICLs) removal involves multiple complex pathways.
- The SNM1 gene family's role in ICL resistance is not fully understood.
- Previous studies implicated ATR in ICL response.
Purpose of the Study:
- To elucidate the precise function of Snm1B/Apollo in DNA interstrand cross-link repair.
- To investigate Snm1B/Apollo's role in cellular sensitivity to DNA damaging agents.
- To determine the specific DNA damage response pathway influenced by Snm1B/Apollo.
Main Methods:
- Human cell knockdown of Snm1B/Apollo.
- Assessing cellular sensitivity to mitomycin C (MMC) and ionizing radiation (IR).
- Analyzing S-phase checkpoint activation and DNA damage signaling pathways (ATM, ATR).
- Investigating protein-protein interactions (Mus81-Eme1, MRN complex, FancD2).
Main Results:
- Snm1B/Apollo knockdown caused hypersensitivity to MMC but not IR.
- Snm1B-deficient cells showed defective S-phase checkpoint response to MMC.
- ATM-mediated checkpoint activation, not ATR, was defective in Snm1B-deficient cells.
- Snm1B/Apollo promotes double-strand break formation and replication fork collapse after ICL damage.
- Snm1B/Apollo interacts with Mus81-Eme1, MRN complex, and FancD2.
Conclusions:
- Snm1B/Apollo is essential for ATM checkpoint activation following ICL damage.
- Snm1B/Apollo plays a critical role in promoting double-strand break formation and replication fork collapse.
- Snm1B/Apollo functions as a key checkpoint and DNA repair protein, interacting with multiple repair complexes.
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