Proteomic Alterations and Metabolic Pathway Modulations Induced by Methyl Methane Sulfonate Treatment in Response to DNA Damage

Abstract

Exposure to methyl methane sulfonate (MMS), an alkylating agent, induces DNA damage, increasing cellular and metabolic sensitivity, leading to cellular demise and a delay in the cell cycle. This delay is attributed to changes in global transcription regulation, resulting in significant alterations in the proteome. Numerous studies have focused on transcriptome changes post-MMS treatment. However, cellular proteomic changes remain underexplored. This brief literature review is based on the assessment of studies obtained from several PubMed, Web of Science, and Scopus databases and Google Scholar using specific keywords. The article is based on manuscripts published between 2005 and 2024. Proteomic analysis identified 53 proteins, with 36 upregulated, 10 downregulated statuses, and a few exhibiting no or negligible changes. MMS exposure reflected changes in the phosphorylation status of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP-II) and a gross change in the transcriptome. Literature also supports the proteome change of the RNAP-II complex and ~1640 peptides, corresponding to 27 interacting proteins and the twelve RNAP-II subunits. The identified proteins were involved in DNA repair and energy pathway modulation. Notably, significant changes were observed in enzymes mostly related to carbohydrate and amino acid metabolism, predominantly, glycolysis, the fate of pyruvate, and the biosynthetic pathways of amino acid metabolism. The available literature supports a co-regulated response to MMS-induced DNA damage involving both DNA repair mechanisms and metabolic pathways.

Keywords

• methyl methane sulfonate
• dna damage
• proteome changes
• metabolic pathways
• transcription regulation
• oxidative stress