Insights into DNA recombination from the structure of a RAD51–BRCA2 complex
The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility.
Altered fidelity of mitotic chromosome transmission in cell cycle mutants of S. cerevisiae.
Thirteen of 14 temperature-sensitive mutants deficient in successive steps of mitotic chromosome transmission (cdc2, 4, 5, 6, 7, 8, 9, 13, 14, 15, 16, 17 and 20) from spindle pole body separation to a late stage of nuclear division exhibited a dramatic increase in the frequency of chromosome loss and/or mitotic recombination when they were grown at their maximum permissive temperatures. The increase in chromosome loss and/or recombination is likely to be due to the deficiency of functional gene product rather than to an aberrant function of the mutant gene product since the mutant alleles are, with one exception, recessive to the wild-type allele for this phenotype. The generality of this result suggests that a delay in almost any stage of chromosome replication or segregation leads to a decrease in the fidelity of mitotic chromosome transmission. In contrast, temperature-sensitive mutants defective in the control step of the cell cycle (cdc28), in cytokinesis (cdc3) or in protein synthesis (ils1) did not exhibit increased recombination or chromosome loss.--Based upon previous results with mutants and DNA-damaging agents in a variety of organisms, we suggest that the induction of mitotic recombination in certain mutants is due to the action of a repair pathway upon nicks or gaps left in the DNA. This interpretation is supported by the fact that the induced recombination is dependent upon the RAD52 gene product, as essential component in the recombinogenic DNA repair pathway. Gene products whose deficiency leads to induced recombination are, therefore, strong candidates for proteins that function in DNA metabolism. Among the mutants that induce recombination are those known to be defective in some aspect of DNA replication (cdc2, 6, 8, 9) as well as some mutants defective in the G2 (cdc13 and 17) and M (cdc5 and 14) phases of the mitotic cycle. We suggest that special aspects of DNA metabolism may be occurring in G2 and M in order to prepare the chromosomes for proper segregation.
genetic algorithm positioning system process control sample size solar cell visible light dna sequence learning object indoor positioning received signal strength statistical process control indoor localization quantum dot statistical proces indoor positioning system count datum hecke algebra factorial design ieee standard binding site escherichia coli weighted moving average knowledge structure statistical quality control poisson structure cell cycle choice behavior econometric model quality level exponentially weighted moving fractional factorial design saccharomyces cerevisiae selection bia affine weyl group statistical process monitoring power conversion efficiency dye-sensitized solar cell charge transport uniform resource identifier learning object metadatum embryonic stem cell moving average control object class dye-sensitized solar reusable learning object linkage disequilibrium quantity discount spatial process spatial econometric population parameter embryonic stem reusable learning object metadatum heterojunction solar cell dna repair location fingerprinting cell development indoor positioning technique spatial econometric model radiation tolerance heterojunction solar genetic linkage signal peptide bulk heterojunction dna segment recombination rate bulk heterojunction solar dna recombination wifi-based indoor localization surface recombination escherichia coli. low-density lipoprotein indoor positioning solution proposed positioning system surface recombination velocity solar cells. neisseria meningitidi genetic heterogeneity learning object review dna break xrcc5 wt allele xrcc5 gene t cell receptor v(d)j recombination v(d)j recombination-activating protein 1 excretory function neuritis, autoimmune, experimental leukemia, b-cell dna sequence rearrangement immunoglobulin class switch recombination immunoglobulin class switching lipoprotein receptor dna breaks, double-stranded telomere maintenance v(d)j recombination genome encoded entity vdj recombinase recombination, genetic crossover (genetic algorithm) meiotic recombination homologous recombination