A5035077989- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Plant Molecular Biology Research
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
- Bacterial Genetics and Biotechnology
- Fungal and yeast genetics research
- Chromosomal and Genetic Variations
- Cancer-related gene regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Plant Reproductive Biology
- Genetic factors in colorectal cancer
The Francis Crick Institute
2018-2024
The University of Tokyo
2012-2018
Yeast cohesin complexes cluster onto long DNA into liquid droplets, which they accomplish by ATP-independent bridging.
Cohesin is a conserved, ring-shaped protein complex that topologically embraces DNA. Its central role in genome organization includes functions sister chromatid cohesion, DNA repair, and transcriptional regulation. loading onto chromosomes requires the Scc2-Scc4 cohesin loader, whose presence on chromatin budding yeast depends RSC remodeling complex. Here we reveal dual of loading. acts as receptor recruits by direct interaction independent remodeling. In addition, required to generate...
Abstract Sequences that form DNA secondary structures, such as G‐quadruplexes (G4s) and intercalated‐Motifs (iMs), are abundant in the human genome play various physiological roles. However, they can also interfere with replication threaten stability. Multiple lines of evidence suggest G4s inhibit replication, but underlying mechanism remains unclear. Moreover, how iMs affect replisome is lacking. Here, we reconstitute physiologically derived structure‐forming sequences to find a single G4...
Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Cohesion establishment requires acetylation of conserved lysine residues by Eco1 acetyltransferase. Here, we explore how is linked to replication. Biochemical reconstitution replication-coupled reveals that transient structures, which form during control reaction. As polymerases complete lagging strand displacement synthesis produces flaps are trimmed result in...
The ring-shaped chromosomal cohesin complex holds sister chromatids together by topological embrace, a prerequisite for accurate chromosome segregation. Cohesin plays additional roles in genome organization, transcriptional regulation and DNA repair. ring includes an ABC family ATPase, but the molecular mechanism which ATPase contributes to function is not yet understood. Here we have purified budding yeast cohesin, as well its Scc2-Scc4 loader complex, biochemically reconstituted...
Concomitant with DNA replication, the ring-shaped cohesin complex encircles both newly synthesized sister chromatids, enabling their faithful segregation during cell divisions. Our molecular understanding of how co-entraps replication products remains incomplete. Here, we reconstitute chromatid cohesion establishment using purified budding yeast proteins. Cohesin rings, initially loaded onto template DNA, remain DNA-bound synthesis and encircle products. Additionally, instigates new...
Abstract Cohesin is a key protein complex that organizes the spatial structure of chromosomes during interphase. Here, we show yeast cohesin shows pronounced clustering on DNA in an ATP-independent manner, exhibiting all hallmarks phase separation. In vitro visualization DNA-cohesin clusters exhibit liquid-like behavior. This includes mutual fusion and reversible dissociation upon depleting concentration, increasing ionic strength, or adding 1,6-hexanediol, conditions disrupt weak...
Abstract The chromosomal cohesin complex establishes sister chromatid cohesion during S phase, which forms the basis for faithful segregation of DNA replication products cell divisions. Cohesion establishment is defective in absence either three non-essential Saccharomyces cerevisiae fork components Tof1-Csm3 and Mrc1. Here, we investigate how these conserved factors contribute to establishment. Mrc1 serve known roles replication, including checkpoint signaling, securing speed, as well...
Summary Understanding how DNA replication forks stall and restart the damage checkpoint prevents irreversible fork collapse in molecular detail are crucial for understanding cells maintain stable genomes they prevent genetic instability that drives cancer. Here we describe reconstitution of stalling with purified budding yeast proteins. After nucleotide depletion, leading strand synthesis quickly stops but CMG helicase continues to unwind Okazaki fragments continue initiate on lagging...
Abstract Sequences that can form DNA secondary structures, such as G-quadruplexes (G4s) and intercalated-Motifs (iMs), are abundant in the human genome play a range of physiological roles. However, they also pose challenge to replication machinery turn threaten stability. Multiple lines evidence suggest G4s interfere with replication, but underlying mechanism remains unclear. Moreover, there is lack how iMs affect replisome. Here, we reconstitute physiologically derived structure-forming...
Abstract Recent genetic studies have revealed a number of novel gene mutations in myeloid malignancies, unmasking an unexpected role deregulated histone modification and DNA methylation neoplasms. However, our knowledge about the spectrum neoplasms is still incomplete. So, we analyzed 50 paired tumor-normal samples using whole exome sequencing, among which identified recurrent involving STAG2, core cohesin component, two other components, including STAG1 PDS5B. Cohesin multimeric protein...