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Updated: Sep 24, 2025
09:29
Author Spotlight: Decoding DNA Repair by Extrachromosomal NHEJ Assay and HR Assays
Published on: February 2, 2024
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Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and
Sebastiano Giallongo1,2, Daniela Řeháková1, Tommaso Biagini3
1International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Stem Cells (Dayton, Ohio)
|May 5, 2022
Summary
The histone variant macroH2A1.1 enhances DNA damage repair (DDR) and improves induced pluripotent stem cell (iPSC) reprogramming by interacting with PARP1 and XRCC1. This isoform shows potential for enhancing iPSC genome stability and therapeutic applications.
Area of Science:
- Epigenetics
- Molecular Biology
- Stem Cell Biology
Background:
- DNA damage repair (DDR) is crucial for maintaining genome integrity.
- Enhancing DDR efficiency can improve induced pluripotent stem cell (iPSC) reprogramming yields.
- Epigenetic regulation of DDR during iPSC reprogramming is not fully understood.
Purpose of the Study:
- To investigate the role of macroH2A1 splicing isoforms (macroH2A1.1 and macroH2A1.2) in regulating DDR during iPSC reprogramming.
- To identify potential interactions between macroH2A1 isoforms and DDR proteins.
Main Methods:
- Utilized GFP-Trap and liquid chromatography-tandem mass spectrometry to identify protein interactions.
- Overexpressed and knocked out macroH2A1.1 in human cell lines and mice.
- Assessed DDR capacity and iPSC reprogramming efficiency in human umbilical vein endothelial cells (HUVECs).
Main Results:
- MacroH2A1.1 exclusively interacted with Poly-ADP Ribose Polymerase 1 (PARP1) and X-ray cross-complementing protein 1 (XRCC1).
- MacroH2A1.1 overexpression enhanced nonhomologous end joining (NHEJ) repair and improved iPSC reprogramming in HUVECs.
- MacroH2A1.1 knockout mice exhibited impaired DDR capacity.
Conclusions:
- MacroH2A1.1, but not macroH2A1.2, acts as a regulator of DDR and enhances iPSC reprogramming.
- MacroH2A1.1 may serve as a promising epigenetic target to improve iPSC genome stability and therapeutic potential.
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