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Interaction of DDB1 with NBS1 in a DNA Damage Checkpoint Pathway.
Interaction of DDB1 with NBS1 in a DNA Damage Checkpoint Pathway.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Dec 05; Vol. 25 (23). Date of Electronic Publication: 2024 Dec 05. - Publication Year :
- 2024
-
Abstract
- Various DNA damage checkpoint control mechanisms in eukaryotic cells help maintain genomic integrity. Among these, NBS1, a key component of the MRE11-RAD50-NBS1 (MRN) complex, is an essential protein involved in the DNA damage response (DDR). In this study, we discovered that DNA damage-binding protein 1 (DDB1) interacts with NBS1. DDB1 is a DDR sensor protein found in UV-induced DNA replication blocks. Through pull-down and immunoprecipitation assays conducted in Xenopus egg extracts and human cell lines, we demonstrated a specific interaction between NBS1 and DDB1. DDB1 was also found to associate with several proteins that interact with NBS1, including DNA topoisomerase 2-binding protein 1 (TopBP1) and Mediator of DNA damage checkpoint protein 1 (MDC1). Notably, the interaction between DDB1 and NBS1 is disrupted in MDC1-depleted egg extracts, indicating that MDC1 is necessary for this interaction. Furthermore, the depletion of DDB1 leads to increased Chk1 activation upon DNA damage. These novel findings regarding the interaction between NBS1 and DDB1 provide new insights into how DDB1 regulates DNA damage pathways.
- Subjects :
- Humans
Animals
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Signal Transducing genetics
Xenopus Proteins metabolism
Xenopus Proteins genetics
Carrier Proteins metabolism
Carrier Proteins genetics
Protein Binding
Trans-Activators metabolism
Trans-Activators genetics
Xenopus laevis
Tumor Suppressor Proteins
Cell Cycle Proteins metabolism
Cell Cycle Proteins genetics
DNA Damage
DNA-Binding Proteins metabolism
DNA-Binding Proteins genetics
Nuclear Proteins metabolism
Nuclear Proteins genetics
Checkpoint Kinase 1 metabolism
Checkpoint Kinase 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39684807
- Full Text :
- https://doi.org/10.3390/ijms252313097