https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/114 Mon, 27 Apr 2026 15:41:21 GMT 2026-04-27T15:41:21Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1546 Title: Pigmented skin exhibits accelerated wound healing compared to the nonpigmented skin in Guinea pig model Authors: Gupta, Rohit; Priya, Anshu; Chowdhary, Manish; Batra, Vineeta V; Jyotsna; Nagarajan, Perumal; Gokhale, Rajesh S; Singh, Archana Abstract: This study investigated and compared the wound healing kinetics of pigmented (PG) and non-pigmented (NP) skin in guinea pigs, focusing on histological and transcriptional changes. Full-thickness wounds created on PG and NP skin were evaluated at various time points post-injury. Fontana-Masson staining and ultrastructural analysis suggested the presence of melanin and melanosomes in PG skin, which coincided with an upregulation of melanogenic genes cKIT, TYR, and DCT. On day 9 post-wound, PG skin exhibited a rapid transition from the inflammatory to proliferative phase, which correlated with the reappearance of epidermal pigmentation whereas the NP skin exhibited a delayed neo-epidermis formation. Furthermore, the study revealed that melanocyte-derived growth factors (conditioned media) positively regulated keratinocyte migration while inhibiting fibroblast differentiation. These effects were more prominent in tyrosine-treated (hyperpigmented) melanocyte-CM as was TGF- β expression. These findings provide valuable insights into the mechanisms underlying skin repair and pigmentation. Sun, 01 Jan 2023 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1546 2023-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1544 Title: Sustained pigmentation causes DNA damage and invokes translesion polymerase Polκ for repair in melanocytes Authors: Ghazi, Madeeha; Khanna, Shivangi; Subramaniam, Yogaspoorthi; Rengaraju, Jeyashri; Sultan, Farina; Gupta, Iti; Sharma, Kanupriya; Chandna, Sudhir; Gokhale, Rajesh S; Natarajan, Vivek T Abstract: Melanin protects skin cells from ultraviolet radiation-induced DNA damage. However, intermediates of eumelanin are highly reactive quinones that are potentially genotoxic. In this study, we systematically investigate the effect of sustained elevation of melanogenesis and map the consequent cellular repair response of melanocytes. Pigmentation increases γH2AX foci, DNA abasic sites, causes replication stress and invokes translesion polymerase Polκ in primary human melanocytes, as well as mouse melanoma cells. Confirming the causal link, CRISPR-based genetic ablation of tyrosinase results in depigmented cells with low Polκ levels. During pigmentation, Polκ activates replication stress response and keeps a check on uncontrolled proliferation of cells harboring melanin-damaged DNA. The mutational landscape observed in human melanoma could in part explain the error-prone bypass of DNA lesions by Polκ, whose absence would lead to genome instability. Thereby, translesion polymerase Polκ is a critical response of pigmenting melanocytes to combat melanin-induced DNA alterations. Our study illuminates the dark side of melanin and identifies (eu)melanogenesis as a key missing link between tanning response and mutagenesis, mediated via the necessary evil translesion polymerase, Polκ. Sun, 01 Jan 2023 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1544 2023-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1521 Title: Histone variant dictates fate biasing of neural crest cells to melanocyte lineage Authors: Raja, Desingu Ayyappa; Subramaniam, Yogaspoorthi; Aggarwal, Ayush; Gotherwal, Vishvabandhu; Babu, Aswini; Tanwar, Jyoti; Motiani, Rajender K; Sivasubbu, Sridhar; Gokhale, Rajesh S; Natarajan, Vivek T Abstract: In the neural crest lineage, progressive fate restriction and stem cell assignment are crucial for both development and regeneration. Whereas fate commitment events have distinct transcriptional footprints, fate biasing is often transitory and metastable, and is thought to be moulded by epigenetic programmes. Therefore, the molecular basis of specification is difficult to define. In this study, we established a role for a histone variant, H2a.z.2, in specification of the melanocyte lineage from multipotent neural crest cells. H2a.z.2 silencing reduces the number of melanocyte precursors in developing zebrafish embryos and from mouse embryonic stem cells in vitro We demonstrate that this histone variant occupies nucleosomes in the promoter of the key melanocyte determinant mitf, and enhances its induction. CRISPR/Cas9-based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby, our study establishes the role of a histone variant upstream of the core gene regulatory network in the neural crest lineage. This epigenetic mark is a key determinant of cell fate and facilitates gene activation by external instructive signals, thereby establishing melanocyte fate identity. Wed, 01 Jan 2020 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1521 2020-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1466 Title: Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77 Authors: Mehdiratta, Kritee; Nain, Sonam; Sharma, Meenakshi; Singh, Shubham; Srivastava, Sonali; Dhamale, Bhushan Dilip; Mohanty, Debasisa; Kamat, Siddhesh S; Natarajan, Vivek T; Sharma, Rakesh; Gokhale, Rajesh S Abstract: Type III polyketide synthases (PKSs) found across Streptomyces species are primarily known for synthesis of a vast repertoire of clinically and industrially relevant secondary metabolites. However, our understanding of the functional relevance of these bioactive metabolites in Streptomyces physiology is still limited. Recently, a role of type III PKS harboring gene cluster in producing alternate electron carrier, polyketide quinone (PkQ) was established in a related member of the Actinobacteria, Mycobacteria, highlighting the critical role these secondary metabolites play in primary cellular metabolism of the producer organism. Here, we report the developmental stage-specific transcriptional regulation of homologous type III PKS containing gene cluster in freshwater Streptomyces sp. strain MNU77. Gene expression analysis revealed the type III PKS gene cluster to be stringently regulated, with significant upregulation observed during the dormant sporulation stage of Streptomyces sp. MNU77. In contrast, the expression levels of only known electron carrier, menaquinone biosynthetic genes were interestingly found to be downregulated. Our liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis of a metabolite extract from the Streptomyces sp. MNU77 spores also showed 10 times more metabolic abundance of PkQs than menaquinones. Furthermore, through heterologous complementation studies, we demonstrate that Streptomyces sp. MNU77 type III PKS rescues a respiratory defect of the Mycobacterium smegmatis type III PKS deletion mutant. Together, our studies reveal that freshwater Streptomyces sp. MNU77 robustly produces novel PkQs during the sporulation stage, suggesting utilization of PkQs as alternate electron carriers across Actinobacteria during dormant hypoxic conditions. IMPORTANCE The complex developmental life cycle of Streptomyces sp. mandates efficient cellular respiratory reconfiguration for a smooth transition from aerated nutrient-rich vegetative hyphal growth to the hypoxic-dormant sporulation stage. Polyketide quinones (PkQs) have recently been identified as a class of alternate electron carriers from a related member of the Actinobacteria, Mycobacteria, that facilitates maintenance of membrane potential in oxygen-deficient niches. Our studies with the newly identified freshwater Streptomyces sp. strain MNU77 show conditional transcriptional upregulation and metabolic abundance of PkQs in the spore state of the Streptomyces life cycle. In parallel, the levels of menaquinones, the only known Streptomyces electron carrier, were downregulated, suggesting deployment of PkQs as universal electron carriers in low-oxygen, unfavorable conditions across the Actinobacteria family. Sun, 01 Jan 2023 00:00:00 GMT https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1466 2023-01-01T00:00:00Z