Related Experiment Video
Updated: Apr 16, 2026
07:46
Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
3.4K
Stemness factor Sall4 is required for DNA damage response in embryonic stem cells
Jianhua Xiong1, Dilyana Todorova1, Ning-Yuan Su1
1Section of Molecular Biology and Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
The Journal of Cell Biology
|March 4, 2015
Summary
Stemness factor Sall4 is crucial for mouse embryonic stem cell (ESC) genomic stability. Sall4 activates DNA double-stranded break (DSB) responses, protecting ESCs from damage and cytotoxicity.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Mouse embryonic stem cells (ESCs) exhibit remarkable genetic stability, preventing genomic abnormalities.
- The mechanisms underlying ESC genomic stability, particularly in response to DNA damage, are not fully understood.
Purpose of the Study:
- To elucidate the role of the stemness factor Sall4 in DNA double-stranded break (DSB) responses in mouse ESCs.
- To identify the molecular mechanisms by which Sall4 contributes to genomic stability in ESCs.
Main Methods:
- Investigated Sall4's role in DNA damage response pathways in mouse ESCs.
- Analyzed Sall4's interaction with key DNA repair proteins, including ATM, Mre11-Rad50-Nbs1 complex, and Baf60a.
- Assessed the impact of Sall4 on DSB-induced cytotoxicity and genomic stability.
Main Results:
- Sall4 is essential for activating Ataxia Telangiectasia Mutated (ATM)-dependent responses to DSBs in mouse ESCs.
- Sall4 is rapidly recruited to DSB sites and stabilizes the Mre11-Rad50-Nbs1 complex, promoting ATM activation.
- Sall4 interacts with Baf60a, a SWI/SNF complex component, facilitating its recruitment to DSB sites.
Conclusions:
- Sall4 plays a critical role in coordinating stemness with DNA damage response in ESCs.
- These findings reveal novel mechanisms ensuring genomic stability during ESC expansion and preventing transmission of abnormalities.
More Related Videos
Related Concept Videos
02:36DNA Damage can Stall the Cell Cycle
10.4K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.4K
02:36DNA Damage Can Stall the Cell Cycle
3.4K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.4K
01:38Nucleotide Excision Repair
5.9K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
5.9K
01:08Nucleotide Excision Repair
42.8K
Overview
42.8K
02:54Nucleosome Remodeling
11.7K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
11.7K
01:14Maintenance of the ES Cell State
2.8K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.8K