Biology subjects

Abe, K. T.

Publications and source records attributed to Abe, K. T..

4 recordsLinked to original sources

bioRxiv2025

Mitotic single-stranded DNA suppression by DDIAS

Incomplete DNA replication and chromosome breakage during mitosis pose major threats to chromosome segregation. The CIP2A-TOPBP1 complex acts to mitigate this peril, but its exact role is not yet understood. Here, we report that DDIAS acts as a DNA-binding effector of the CIP2A-TOPBP1 complex. DDIAS directly interacts with TOPBP1 and the disruption of this interaction or inactivation of its single-stranded DNA (ssDNA)-binding ability impairs genome integrity and causes synthetic lethality with BRCA1 and BRCA2 deficiency. DDIAS does not promote the putative end-tethering function of CIP2A-TOPBP1 but rather acts to suppress ssDNA during mitosis. This role is emphasized by a pronounced genetic interaction between the genes coding for DDIAS and DNA polymerase (. We conclude that DDIAS defines a mitotic DNA damage response that mitigates the threat of mitotic ssDNA arising from DNA replication stress, which we infer is a liability to accurate chromosome segregation. (144 words).

molecular biology↗

bioRxiv2023

Evolution of chromosome arm aberrations in breast cancer through genetic network rewiring

The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize the evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. TCGA data analysis showed recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a unique panel of 23 primary tumor/patient-derived xenograft basal breast cancers revealed early evolution of chr4p deletion. Mechanistically we show that Chr4p loss is associated with enhanced proliferation. Gene function studies identified an unknown gene, C4orf19, within chr4p, which suppressed proliferation when overexpressed and is a novel member of a PDCD10-GCKIII kinase module, we name as PGCA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames, identified chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner implicating network interactions. Together this sheds light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.

genomics↗

bioRxiv2022

Functional diversification despite structural congruence in the HipBST toxin-antitoxin system of Legionella pneumophila

Toxin-antitoxin (TA) systems are abundant genetic modules in bacterial chromosomes and on mobile elements. They are often patchily distributed and their physiological functions remain poorly understood. Here, we characterize a TA system in Legionella pneumophila that is highly conserved across Legionella species. This system is distantly related to Escherichia coli HipBST and we demonstrate that it is a functional tripartite TA system (denoted HipBSTLp). We identify HipBSTLp homologs in diverse taxa, yet in the Gammaproteobacteria these are almost exclusively found in Legionella species. Notably, the toxin HipTLp was previously reported to be a pathogenic effector protein that is translocated by L. pneumophila into its eukaryotic hosts. Contrary to this, we find no signal of HipTLp translocation beyond untranslocated control levels and make several observations consistent with a canonical role as a bacterial toxin. We present structural and biochemical insights into the regulation and neutralization of HipBSTLp, and identify key variations between this system and HipBSTEc. Finally, we show that the target of HipTLp is likely not conserved with any characterized HipA or HipT toxin. This work serves as a unique comparison of a TA system across bacterial species and illustrates the molecular diversity that exists within a single TA family.

microbiology↗

bioRxiv2019

A proximity biotinylation map of a human cell

Compartmentalization is a defining characteristic of eukaryotic cells, partitioning cellular processes into discrete subcellular locations. High throughput microscopy1 and biochemical fractionation coupled with mass spectrometry2-6 have helped to define the proteomes of a variety of organelles and macromolecular structures. However, many other intracellular compartments have remained refractory to such approaches, due for example to difficulty in purifying non-membrane bound structures. Proximity-dependent biotinylation techniques such as BioID provide an alternative approach for defining the composition of cellular compartments in living cells7-10. Here we present a BioID-based map of a human cell based on 192 markers from 32 different subcellular compartments, comprising 35,902 high confidence proximity interactions, and defining the intracellular locations of 4,145 unique proteins in HEK 293 cells. Our localization predictions meet or exceed previous-approaches, with higher specificity, and enabled the discovery of proteins at the mitochondrial outer membrane-endoplasmic reticulum (ER) interface that are critical for mitochondrial homeostasis. Based on this dataset, we have established humancellmap.org as a community resource that provides online tools for localization analysis of user BioID data, and demonstrate how this resource can be used to better understand BioID datasets.

molecular biology↗