Interaction of DDB1 with NBS1 in a DNA Damage Checkpoint Pathway

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 prot...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-12, Vol.25 (23), p.13097
Main Authors: Lim, Hoe Eun, Lim, Hee Jung, Yoo, Hae Yong
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antibodies
Ataxia
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cells
Checkpoint Kinase 1 - genetics
Checkpoint Kinase 1 - metabolism
DNA
DNA Damage
DNA repair
DNA replication
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Genetic research
Humans
Kinases
Mass spectrometry
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Protein Binding
Proteins
Radiation
Scientific imaging
Trans-Activators - genetics
Trans-Activators - metabolism
Tumor Suppressor Proteins
Xenopus laevis
Xenopus Proteins - genetics
Xenopus Proteins - metabolism
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms252313097