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Published on: January 31, 2018
PRDM2 and DNA damage response: phosphoregulatory signaling insights
Vaishnavi Gopalakrishnan1, Althaf Mahin1, Leona Dcunha1
1Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, 575018 Karnataka India.
Abstract:
PRDM2 is a histone methyltransferase that regulates gene expression through histone H3 lysine 9 methylation. It is involved in the DNA damage response by controlling chromatin remodeling and maintaining genomic integrity. However, the functional relevance of its phosphorylation remains poorly understood. To address this gap, we systematically characterized PRDM2 phosphosites and their associated phospho-signaling networks using large-scale cellular phosphoproteomics data curated from PubMed-indexed articles. Frequency-based ranking revealed Ser643 and Ser421 as predominant phosphosites, detected across 334 and 141 qualitative datasets and 70 and 47 differential cellular phosphoproteomics datasets, respectively. To explore PRDM2-associated phospho-signaling, expression co-regulation analysis was performed to identify phosphosites in other proteins exhibiting consistently similar or opposing expression patterns relative to the predominant PRDM2 phosphosites. This analysis identified 1,251 phosphosites in other proteins showing high-confidence expression co-regulation with PRDM2 Ser421 and 715 phosphosites with PRDM2 Ser643. Functional enrichment revealed significant associations with cell cycle regulation, chromatin organization, RNA processing, and DNA damage response (DDR) pathways. Notably, phosphosites in 30 DDR-related proteins positively co-regulated with Ser643 and 28 with Ser421. Additionally, ATR was identified as a potential kinase predicted to phosphorylate the predominant PRDM2 sites, and its phosphosites exhibited consistent expression co-regulation with PRDM2 sites. Collectively, this study establishes a comprehensive phospho-signaling framework for PRDM2, uncovering its strong association with DNA damage response pathways and providing mechanistic insights into its regulatory network. Clinical trial registration: This study is not part of any clinical trial.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s13205-026-04782-3.
Insights
This study maps PRDM2 phosphorylation sites and their signaling networks, revealing a strong link to DNA damage response pathways and identifying ATR as a potential kinase. This work clarifies PRDM2
Area of Science:
- Molecular Biology
- Epigenetics
- Proteomics
Background:
- PRDM2 is a histone methyltransferase crucial for gene regulation and DNA damage response.
- The functional role of PRDM2 phosphorylation is largely unknown.
- Understanding PRDM2 phosphorylation is key to elucidating its role in maintaining genomic integrity.
Purpose of the Study:
- To systematically characterize PRDM2 phosphosites and their associated signaling networks.
- To identify key PRDM2 phosphorylation sites and their regulatory partners.
- To uncover the functional implications of PRDM2 phosphorylation in cellular processes.
Main Methods:
- Large-scale cellular phosphoproteomics data analysis from PubMed-indexed articles.
- Frequency-based ranking to identify predominant PRDM2 phosphosites (Ser643, Ser421).
- Expression co-regulation analysis to map associated phospho-signaling networks and identify potential kinases (e.g., ATR).
Main Results:
- Ser643 and Ser421 identified as predominant PRDM2 phosphosites across numerous datasets.
- Over 1,251 and 715 phosphosites in other proteins co-regulated with PRDM2 Ser421 and Ser643, respectively.
- Significant enrichment of co-regulated phosphosites in cell cycle, chromatin organization, RNA processing, and DNA damage response (DDR) pathways, with strong links to DDR proteins.
Conclusions:
- A comprehensive PRDM2 phospho-signaling framework has been established.
- PRDM2 phosphorylation is strongly associated with DNA damage response pathways.
- ATR kinase is a potential regulator of PRDM2 phosphorylation, providing mechanistic insights into its network.
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