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The lysosomal trafficking regulator (LYST) protein is responsive to cell-cycle progression and DNA damage
Jacob Zbinden, PhD; Gabriel Mirhaidari, PhD; Christopher Breuer, MD; Jenny C. Barker, MD, PhD
Nationwide Children's Hospital
2022-01-15
Presenter: Jacob Zbinden
Affidavit:
This abstract represents 100% original work from the corresponding author Jenny C Barker, co-faculty authors and the two students listed.
Director Name: Gregory Pearson
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
PURPOSE: The lysosomal trafficking regulator (LYST) gene influences the size, location and degranulation of lysosomes through an unidentified mechanism. LYST has been recently implicated in multiple cancer types and in tissue healing abnormalities. We sought to improve the characterization of LYST by identifying factors that affect the cellular localization of the LYST protein.
METHODS: Primary fibroblast cultures were derived from wild-type (WT) and LYST-mutant Beige (Bg) mice. RNA-sequencing was utilized to determine effects of LYST mutation on cellular processes. LYST protein localization was determined with high resolution immunofluorescence microscopy. Cell cycle assignment (G1/S/G2) was performed based on quantification of DAPI nuclear staining relative to nuclear area.
RESULTS: RNA-sequencing with pathway analysis identified disruption of pathways involved in DNA repair, cell division, and cell cycle progression in Bg fibroblasts compared to WT fibroblasts. LYST was identified as both a nuclear and a peri-nuclear cytoplasmic protein, displaying capacity for nuclear-cytoplasmic shuttling. While in the nucleus, LYST localized with the regulatory kinase Casein-kinase 2. LYST had significantly increased nuclear versus cytoplasmic localization during G2 indicating a previously undescribed relationship between LYST and cell cycle progression. The LYST gene was upregulated in the presence of UV-induced DNA damage.
CONCLUSIONS: Improved understanding of factors that influence the function, expression, and localization of LYST remains lacking. This is increasingly relevant as LYST is identified in disease processes, such as a cancer prognostic marker and in wound healing. Our results indicate a novel role for LYST in normal DNA repair and cell cycle progression.
