Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Unlabelled: WDR76 is a multifunctional protein involved in many cellular functions. With a diverse and complicated protein interaction network, dissecting the structure and function of specific WDR76 complexes is needed. We previously demonstrated the ability of the Serial Capture Affinity Purification (SCAP) method to isolate specific complexes by introducing two proteins of interest as baits at the same time. Here, we applied SCAP to dissect a subpopulation of WDR76 in complex with SPIN1, a histone marker reader that specifically recognizes trimethylated histone H3 lysine4 (H3K4me3). In contrast to the SCAP analysis of the SPIN1:SPINDOC complex, H3K4me3 was copurified with the WDR76:SPIN1 complex. In combination with crosslinking mass spectrometry, we built an integrated structural model of the complex which revealed that SPIN1 recognized the H3K4me3 epigenetic mark while interacting with WDR76. Lastly, interaction network analysis of copurifying proteins revealed the potential role of the WDR76:SPIN1 complex in the DNA damage response.

Teaser: In contrast to the SPINDOC/SPIN1 complex, analyses reveal that the WDR76/SPIN1 complex interacts with core histones and is involved in DNA damage.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915617PMC
http://dx.doi.org/10.1101/2023.01.31.526478DOI Listing

Publication Analysis

Top Keywords

dna damage
12
wdr76spin1 complex
12
serial capture
8
capture affinity
8
affinity purification
8
integrated structural
8
complex
8
interaction network
8
purification integrated
4
structural modeling
4

Similar Publications

Mechanistic roles of long non-coding RNAs in DNA damage response and genome stability.

Mutat Res Rev Mutat Res

September 2025

Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:

To maintain genomic stability, cells have evolved complex mechanisms collectively known as the DNA damage response (DDR), which includes DNA repair, cell cycle checkpoints, apoptosis, and gene expression regulation. Recent studies have revealed that long non-coding RNAs (lncRNAs) are pivotal regulators of the DDR. Beyond their established roles in recruiting repair proteins and modulating gene expression, emerging evidence highlights two particularly intriguing functions.

View Article and Find Full Text PDF

Clonal hematopoiesis, originally identified as a precursor to hematologic malignancies, has emerged as a significant factor in various nonmalignant diseases. Recent research highlights how somatic mutations in hematopoietic stem cells lead to the expansion of circulating mutated immune cells that exert profound effects on organ function and disease progression. These mutated clones display altered inflammatory profiles and tissue-specific functional consequences, contributing to various diseases including atherosclerotic cardiovascular disease, osteoporosis, heart failure, and neurodegenerative conditions.

View Article and Find Full Text PDF

Fanconi Anemia (FA) is a heritable syndrome characterized by DNA damage repair deficits, frequent malformations and a significantly elevated risk of bone marrow failure, leukemia, and mucosal head and neck squamous cell carcinomas (HNSCC). Hematopoietic stem cell gene therapy can prevent marrow failure and lower leukemia risk, but mucosal gene therapy to lower HNSCC risk remains untested. Major knowledge gaps include an incomplete understanding of how rapidly gene-corrected cellular lineages could spread through the oral epithelium, and which delivery parameters are critical for ensuring efficient gene correction.

View Article and Find Full Text PDF

The RecBC complex protects single-stranded DNA gaps during lesion bypass.

Proc Natl Acad Sci U S A

September 2025

Cancer Research Center of Marseille: Team DNA Damage and Genome Instability|CNRS, Inserm, Institut Paoli-Calmettes, Aix Marseille Université, Marseille 13009, France.

Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks.

View Article and Find Full Text PDF

The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on REV1's ability to recruit inserter TLS polymerases and the POLζ extender polymerase, enables cancer cells to bypass DNA lesions while introducing mutations that likely contribute to the development of chemotherapy resistance and secondary malignancies. Targeting this pathway represents a promising therapeutic strategy. Here, we demonstrate that the expression of the C-terminal domain (CTD) of human REV1, a ca.

View Article and Find Full Text PDF