Abstract:
:Kinesin-1 is a motor protein that moves stepwise along microtubules by employing dimerized kinesin heavy chain (Khc) subunits that alternate cycles of microtubule binding, conformational change, and ATP hydrolysis. Mutations in the Drosophila Khc gene are known to cause distal paralysis and lethality preceded by the occurrence of dystrophic axon terminals, reduced axonal transport, organelle-filled axonal swellings, and impaired action potential propagation. Mutations in the equivalent human gene, Kif5A, result in similar problems that cause hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth type 2 (CMT2) distal neuropathies. By comparing the phenotypes and the complementation behaviors of a large set of Khc missense alleles, including one that is identical to a human Kif5A HSP allele, we identified three routes to suppression of Khc phenotypes: nutrient restriction, genetic background manipulation, and a remarkable intramolecular complementation between mutations known or likely to cause reciprocal changes in the rate of microtubule-stimulated ADP release by kinesin-1. Our results reveal the value of large-scale complementation analysis for gaining insight into protein structure-function relationships in vivo and point to possible paths for suppressing symptoms of HSP and related distal neuropathies.
journal_name
Geneticsjournal_title
Geneticsauthors
Djagaeva I,Rose DJ,Lim A,Venter CE,Brendza KM,Moua P,Saxton WMdoi
10.1534/genetics.112.140798subject
Has Abstractpub_date
2012-09-01 00:00:00pages
173-83issue
1eissn
0016-6731issn
1943-2631pii
genetics.112.140798journal_volume
192pub_type
杂志文章相关文献
GENETICS文献大全abstract::Nontandem terminal chromosome duplications derived from N. crassa translocation T(I-->VI)NM103 give rise mitotically to some daughter nuclei which have become euploid by loss of one or the other of the two duplicated segments. Loss of the segment in normal sequence occurs as often as loss of the translocated segment. ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::The vacuolar hydrolase protease B in Saccharomyces cerevisiae is synthesized as an inactive precursor (Prb1p). The precursor undergoes post-translational modifications while transiting the secretory pathway. In addition to N- and O-linked glycosylations, four proteolytic cleavages occur during the maturation of Prb1p....
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::A coalescent theory for a sample of DNA sequences from a partially selfing diploid population and an algorithm for simulating such samples are developed in this article. Approximate formulas are given for the expectation and the variance of the number of segregating sites in a sample of k sequences from n individuals....
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Arabidopsis seedlings repair UV-induced DNA damage via light-dependent and independent pathways. The mechanism of the "dark repair" pathway is still unknown. To determine the number of genes required for dark repair and to investigate the substrate-specificity of this process we isolated mutants with enhanced sensitiv...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantl...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::Self-incompatibility (SI) is a genetic system found in some hermaphrodite plants. Recognition of pollen by pistils expressing cognate specificities at two linked genes leads to rejection of self pollen and pollen from close relatives, i.e., to avoidance of self-fertilization and inbred matings, and thus increased outc...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.111.127399
更新日期:2011-07-01 00:00:00
abstract::The rate of decline in reproductive fitness in populations of Drosophila melanogaster inbred at an initial rate of approximately 1% per generation has been investigated under both competitive and noncompetitive conditions. Breeding population size was variable in the inbred lines with an estimated harmonic mean of 66....
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Combined with a system for identifying each of the chromosomes in a genome, visualizing the location of individual genetic loci by fluorescence in situ hybridization (FISH) would aid in assembling physical and genetic maps. Previously, large genomic clones have been successfully used as FISH probes onto somatic chromo...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.065573
更新日期:2007-03-01 00:00:00
abstract::BTB-zinc finger transcription factors play many important roles in metazoan development. In these proteins, the BTB domain is critical for dimerization and for recruiting cofactors to target genes. Identification of these cofactors is important for understanding how BTB-zinc finger proteins influence transcription. He...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.109.111591
更新日期:2010-04-01 00:00:00
abstract::The distribution of genetic polymorphisms in a population contains information about evolutionary processes. The Poisson random field (PRF) model uses the polymorphism frequency spectrum to infer the mutation rate and the strength of directional selection. The PRF model relies on an infinite-sites approximation that i...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.108.087361
更新日期:2008-12-01 00:00:00
abstract::We demonstrate that the previously described gene Androgen binding protein (Abp; Dlouhy and Karn, 1984) codes for the Alpha subunit of ABP and rename the locus Androgen binding protein alpha (Abpa). A study of recombinant inbred strains demonstrates that Abpa is located on chromosome 7 near Glucose phosphate isomerase...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::Two Podospora mutants carrying mutations modE and modF were persumed to be quiescent defective, because, when grown under glucose limitation, they differed from the wild-type strain in an excess of dry weight production and a reduction of cell survival. New insight on the action of modE and modF mutations was provided...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Parameters of continuous distributions of effects and rates of spontaneous mutation for relative viability in Drosophila are estimated by maximum likelihood from data of two published experiments on accumulation of mutations on protected second chromosomes. A model of equal mutant effects gives a poor fit to the data ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Secondary trisomics and telotrisomics representing the 12 chromosomes of rice were isolated from the progenies of primary trisomics. A large population of each primary trisomic was grown. Plants showing variation in gross morphology compared to the primary trisomics and disomic sibs were selected and analyzed cytologi...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::The POL3 encoded catalytic subunit of DNA polymerase delta possesses a highly conserved C-terminal cysteine-rich domain in Saccharomyces cerevisiae. Mutations in some of its cysteine codons display a lethal phenotype, which demonstrates an essential function of this domain. The thermosensitive mutant pol3-13, in which...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::A wheat (Triticum aestivum L. emend Thell) disomic addition line (2n = 6x = 44), SH1-152-2, with a pair of Elytrigia pontica (Podp.) Holub 2n = 10x = 70 [syn. Agropyron elongatum (Host) P.B.] chromosomes controlling blue aleurone color was crossed with a short-statured spring wheat ;Sonora 64' (T. aestivum). Isoline p...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Automated image acquisition, a custom analysis algorithm, and a distributed computing resource were used to add time as a third dimension to a quantitative trait locus (QTL) map for plant root gravitropism, a model growth response to an environmental cue. Digital images of Arabidopsis thaliana seedling roots from two ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.113.153346
更新日期:2013-11-01 00:00:00
abstract::The Drosophila oocyte develops from a cluster of 16 interconnected cells that derive from a common progenitor. One of these cells, the oocyte, arrests in meiosis. The other cells endoreplicate their DNA and produce mRNAs and proteins that they traffic to the oocyte along a polarized microtubule cytoskeleton shared by ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::During meiosis homologous chromosomes replicate once, pair, experience recombination, and undergo two rounds of segregation to produce haploid meiotic products. The rec8(+), rec10(+), and rec11(+) genes of the fission yeast Schizosaccharomyces pombe exhibit similar specificities for meiotic recombination and rec8(+) i...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Strand misalignments at DNA repeats during replication are implicated in mutational hotspots. To study these events, we have generated strains carrying mutations in the Escherichia coli chromosomal lacZ gene that revert via deletion of a short duplicated sequence or by template switching within imperfect inverted repe...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.111.127746
更新日期:2011-06-01 00:00:00
abstract::A model of the evolution of a transposable element family in a Mendelian host population is proposed that incorporates heritable phenotypic mutations in the elements. The temporal behavior of the numbers of mutant and wild-type elements is studied, and the expected extinction time of the transposable element family is...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Mathematical models are presented for the evolution of postmating and premating reproductive isolation. In the case of postmating isolation it is assumed that hybrid sterility or inviability is caused by incompatibility of alleles at one or two loci, and evolution of reproductive isolation occurs by random fixation of...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::The initiation of growth cessation and dormancy represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees. The most important environmental cue regulating the initiation of dormancy is a shortening of the photoperiod and phytochrome genes have been implicated in short...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.105.047522
更新日期:2006-03-01 00:00:00
abstract::We define a new gene, SRD1, involved in the processing of pre-rRNA to mature rRNA. The SRD1 gene was identified by selecting for second-site suppressors of the previously described rrp1-1 mutation. The rrp1-1 mutation causes temperature-sensitive growth, a conditional defect in processing of 27S pre-rRNA to mature 25S...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::An elevated mutation rate can provide cells with a source of mutations to adapt to changing environments. We identified a negative epistatic interaction involving naturally occurring variants in the MLH1 and PMS1 mismatch repair (MMR) genes of Saccharomyces cerevisiae We hypothesized that this MMR incompatibility, cre...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.116.199513
更新日期:2017-04-01 00:00:00
abstract::Biological robustness, the ability of an organism to maintain a steady-state output as genetic or environmental inputs change, is critical for proper development. MicroRNAs have been implicated in biological robustness mechanisms through their post-transcriptional regulation of genes and gene networks. Previous resear...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.115.179184
更新日期:2015-08-01 00:00:00
abstract::Crossover interference in meiosis is often modeled via stationary renewal processes. Here we consider a new model to incorporate the known biological feature of "obligate chiasma" whereby in most organisms each bivalent almost always has at least one crossover. The initial crossover is modeled as uniformly distributed...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.070235
更新日期:2007-07-01 00:00:00
abstract::A simple method of replica plating has been used to isolate mutants of Neurospora crassa that have increased sensitivity to methyl methanesulfonate (MMS) and/or to histidine. Twelve mutants with increased sensitivity to MMS and one mutant with increased sensitivity to histidine showed Mendelian segregation of the muta...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1981-02-01 00:00:00
abstract::DNA topoisomerases, enzymes that alter the superhelicity of DNA, have been implicated in such critical cellular functions as transcription, DNA replication, and recombination. In the yeast Saccharomyces cerevisiae, a null mutation in the gene encoding topoisomerase I (TOP1) causes elevated levels of mitotic recombinat...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The rate of microsatellite mutation is dependent upon both the allele length and the repeat motif, but the exact nature of this relationship is still unknown. We analyzed data on the inheritance of human Y-chromosomal microsatellites in father-son duos, taken from 24 published reports and comprising 15,285 directly ob...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.111.132308
更新日期:2011-12-01 00:00:00