Related Experiment Video
Updated: Apr 19, 2026
Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks
Published on: November 10, 2016
Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response
Alberto Ciccia1, Jen-Wei Huang2, Lior Izhar3
1Department of Genetics and Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Harvard University Medical School, Boston, MA 02115; Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032; and selledge@genetics.med.harvard.edu ac3685@columbia.edu.
Abstract:
The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.
Insights
This study reveals that TCOF1, a protein linked to Treacher Collins syndrome, interacts with DNA damage response (DDR) factors NBS1 and ATM. This interaction helps maintain genomic integrity by regulating ribosomal DNA transcription after DNA damage.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The DNA damage response (DDR) is crucial for maintaining genomic integrity.
- DDR regulates diverse cellular processes including DNA repair and transcription.
- NBS1 is a key DDR factor, while TCOF1 is a nucleolar protein involved in rDNA transcription and mutated in Treacher Collins syndrome.
Purpose of the Study:
- To investigate the interaction between NBS1 and TCOF1 within the DDR pathway.
- To elucidate the role of TCOF1 in the DDR and its impact on genomic integrity.
Main Methods:
- Immunofluorescence to track protein localization.
- Phosphorylation site analysis.
- Cellular resistance assays to DNA damaging agents.
Main Results:
- NBS1 relocalizes to nucleoli post-DNA damage, dependent on TCOF1, casein kinase II, and ATM.
- A specific ATM phosphorylation site on NBS1 is essential for its nucleolar relocalization.
- TCOF1 enhances cellular resistance to DNA damaging agents.
Conclusions:
- TCOF1 functions as a DDR factor, cooperating with ATM and NBS1.
- This cooperation suppresses aberrant rDNA transcription and preserves genomic integrity following DNA damage.
Related Concept Videos
01:38Nucleotide Excision Repair
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...
01:08Nucleotide Excision Repair
01:08Nucleotide Excision Repair
02:10Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
02:27Base-pairing and DNA Repair
02:25Overview of DNA Repair
Chemically...