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- Sciencedirect from 1997, Proquest, Rcgp, Gale, CSA, and Ingenta
Interaction of Chk1 with Treslin Negatively Regulates the Initiation of Chromosomal DNA Replication
Molecular Cell (2014)We demonstrate that Treslin is also a critical locus for negative regulatory mechanisms that suppress initiation. We found that the checkpoint-regulatory kinase Chk1 associates specifically with a C-terminal domain of Treslin (designated TRCT). Mutations in the TRCT domain abolish binding of Chk1 to...
Erk2 Phosphorylation of Drp1 Promotes Mitochondrial Fission and MAPK-Driven Tumor Growth
Molecular Cell (2009)We show that expression of oncogenic Ras or direct activation of the MAPK pathway leads to increased mitochondrial fragmentation and that blocking this phenotype, through knockdown of the mitochondrial fission-mediating GTPase Drp1, inhibits tumor growth. This fission is driven by Erk2-mediated phos...
Noncovalent Interactions with SUMO and Ubiquitin Orchestrate Distinct Functions of the SLX4 Complex in Genome Maintenance.
We show that SLX4 binds SUMO-2/3 chains via SUMO-interacting motifs (SIMs). The SIMs of SLX4 are dispensable for ICL repair but important for processing CPT-induced replication intermediates, suppressing fragile site instability, and localizing SLX4 to ALT telomeres. The localization of SLX4 to lase...
Extracellular Vesicles from Neural Stem Cells Transfer IFN-γ via Ifngr1 to Activate Stat1 Signaling in Target Cells
BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing.
We show that BS69 selectively recognizes histone variant H3.3 lysine 36 trimethylation (H3.3K36me3) via its chromatin-binding domains. We further identify BS69 association with RNA splicing regulators, including the U5 snRNP components of the spliceosome, such as EFTUD2. Remarkably, RNA sequencing s...
Ubiquitin chain elongation requires E3-dependent tracking of the emerging conjugate.
We show that the RING-E3 APC/C catalyzes chain elongation by strongly increasing the affinity of its E2 for the distal acceptor ubiquitin in a growing conjugate. This function of the APC/C requires its coactivator as well as conserved residues of the E2 and ubiquitin. APC/C's ability to track the ti...
circRNA Biogenesis Competes with Pre-mRNA Splicing
We identified in neuronal tissues, we provide evidence that animal circRNAs are generated cotranscriptionally and that their production rate is mainly determined by intronic sequences. We demonstrate that circularization and splicing compete against each other. These mechanisms are tissue specific a...
Dynamic RNA Modifications in Posttranscriptional Regulation
We summarize examples of dynamic RNA modifications that affect biological functions. We further propose that reversible modifications might occur on tRNA, rRNA, and other noncoding RNAs to regulate gene expression analogous to the reversible mRNA methylation....
Chromosomal translocations in human cells are generated by canonical nonhomologous end-joining.
We used designer nucleases (ZFNs, TALENs, and CRISPR/Cas9) to introduce DSBs on two chromosomes to study translocation joining mechanisms in human cells. Remarkably, translocations were altered in cells deficient for LIG4 or its interacting protein XRCC4. Translocation junctions had significantly lo...
Chromatin reader Brd4 functions in Ig class switching as a repair complex adaptor of nonhomologous end-joining.
We show that the acetylated histone reader Brd4 is critical for nonhomologous end-joining (NHEJ) repair of AID- and I-SceI-induced DNA breaks. Brd4 was recruited to the DNA break regions, and its depletion from the chromatin caused CSR impairment without affecting the DNA break generation. Inhibitio...