Biology subjects

Chao, J. T.

Publications and source records attributed to Chao, J. T..

2 recordsLinked to original sources

bioRxiv2020

Sentinel Interaction Mapping (SIM) - A generic approach for the functional analysis of human disease gene variants using yeast

Advances in sequencing technology have led to an explosion in the number of known genetic variants of human genes. A major challenge is to now determine which of these variants contribute to diseases as a result of their effect on gene function. Here we describe a generic approach using the yeast Saccharomyces cerevisiae to quickly develop gene-specific in vivo assays that can be used to quantify the level of function of a genetic variant. Using Synthetic Dosage Lethality screening, "sentinel" yeast strains are identified that are sensitive to overexpression of a human disease gene. Variants of the gene can then be functionalized in high-throughput fashion through simple growth assays using either solid or liquid media. Sentinel Interaction Mapping (SIM) has the potential to create functional assays for the large majority of human disease genes that do not have a yeast orthologue. Using the tumour suppressor gene PTEN as an example, we show that SIM assays can provide a fast and economical means to screen a large number of genetic variants.

genomics↗

bioRxiv2019

Transfer of Septin Rings to Cytokinetic Remnants Directs Age-Sensitive ER stress Surveillance Cell Cycle Re-entry

During cell division, cells must actively pass on organelles. Previously, we discovered the endoplasmic reticulum (ER) stress surveillance (ERSU) pathway that ensures the inheritance of functional ER. Activation of the ERSU causes the septin ring to mislocalize, which blocks ER inheritance and cytokinesis. Here, we found that the septin ring mislocalizes to previously utilized cell division sites called cytokinetic remnants (CRMs). The transfer of the septin ring to CRMs requires Nba1, a negative polarity component that normally prevents septin ring formation at CRMs. Furthermore, septin ring movement to CRMs relies on the ERSU component Slt2, which is recruited by binding Bem1. During ER stress, Bem1 also binds the GTP exchange factor Cdc24, without activating Cdc42, a GTPase that normally establishes polarized growth. Failure to translocate septin rings to CRMs delays the cells ability to re-enter cell division when ER homeostasis is re-established. Thus, ER stress considers the history of previous cell cycle for future cell cycle re-entry upon ER stress recovery.

cell biology↗