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- Sciencedirect from 1997, Proquest, Rcgp, Gale, CSA, and Ingenta
Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.
We report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT...
Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1.
We crystallized the full-length human Dmc1 protein and solved the structure of the Dmc1 octameric ring. The monomeric structure of the Dmc1 protein closely resembled those of the human and archaeal Rad51 proteins. In addition to the polymerization motif that was previously identified in the Rad51 pr...
Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene, Brca2.
We report that inactivation of cell cycle checkpoints responsive to mitotic spindle disruption, by mutant forms of p53 or Bub1, relieves growth arrest and initiates neoplastic transformation in primary cells homozygous for truncated Brca2. Tumors from Brca2-deficient animals exhibit dysfunction of t...
Determinants of heterochromatic siRNA biogenesis and function.
We show that convergent antisense transcription and availability of the Dicer ribonuclease are the key determinants for primary siRNA generation. Surprisingly, Dicer makes dual contributions to heterochromatin formation, promoting histone H3 lysine 9 methylation independently of its catalytic activi...
Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity.
We conducted a functional RNAi screen for HDMs and identified five potential HDMs essential for mouse ESC identity. In-depth analyses demonstrate that the closely related HDMs Jmjd2b and Jmjd2c are necessary for self-renewal of ESCs and induced pluripotent stem cell generation. Genome-wide occupancy...
Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically disordered neurospora clock protein FRQ.
Protein conformation dictates a great deal of protein function. A class of naturally unstructured proteins, termed intrinsically disordered proteins (IDPs), demonstrates that flexibility in structure can be as important mechanistically as rigid structure. At the core of the circadian transcription/t...
Genome-wide consequences of deleting any single gene.
We analyzed the yeast knockout collection for secondary mutations of functional consequence. Unlike wild-type, most gene knockout strains were found to have one additional mutant gene affecting nutrient responses and/or heat-stress-induced cell death. Moreover, independent knockouts of the same gene...
HDAC5--a critical player in the p53 acetylation network.
In this issue of Molecular Cell, Sen et al. (2013) identify HDAC5 as a deacetylase with specificity for the K120 site of p53, a key residue of p53 that undergoes acetylation after DNA damage and regulates target gene selection. Copyright © 2013 Elsevier Inc. All rights reserved.
A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress.
We present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains ∼250,000 negative and positive genetic interaction scores and identifies a molecular crosstalk of protein quality control p...
MsrB1 and MICALs Regulate Actin Assembly and Macrophage Function via Reversible Stereoselective Methionine Oxidation
We report that in conjunction with Mical proteins, methionine-R-sulfoxide reductase B1 (MsrB1) regulates mammalian actin assembly via stereoselective methionine oxidation and reduction in a reversible, site-specific manner. Two methionine residues in actin are specifically converted to methionine-R-...