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Biomedical subjects

C R Adams

Publications and source records attributed to C R Adams.

13 recordsLinked to original sources

The RCAF complex mediates chromatin assembly during DNA replication and repair.

Chromatin assembly is a fundamental biological process that is essential for the replication and maintenance of the eukaryotic genome. In dividing cells, newly synthesized DNA is rapidly assembled into chromatin by the deposition of a tetramer of the histone proteins H3 and H4, followed by the deposition of two dimers of histones H2A and H2B to complete the nucleosome-the fundamental repeating unit of chromatin. Here we describe the identification, purification, cloning, and characterization of replication-coupling assembly factor (RCAF), a novel protein complex that facilitates the assembly of nucleosomes onto newly replicated DNA in vitro. RCAF comprises the Drosophila homologue of anti-silencing function 1 protein ASF1 and histones H3 and H4. The specific acetylation pattern of H3 and H4 in RCAF is identical to that of newly synthesized histones. Genetic analyses in Saccharomyces cerevisiae demonstrate that ASF1 is essential for normal cell cycle progression, and suggest that RCAF mediates chromatin assembly after DNA replication and the repair of double-strand DNA damage in vivo.

Amino Acid Sequence↗

The boundaries of the silenced HMR domain in Saccharomyces cerevisiae.

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains that provide a mechanism to compact the DNA as well as delineate independent units of gene activity. It is believed that insulator/boundary elements separate these domains. Here we report the identification and characterization of boundary elements that flank the transcriptionally repressed HMR locus in the yeast Saccharomyces cerevisiae. Deletion of these boundary elements led to the spread of silenced chromatin, whereas the ectopic insertion of these elements between a silencer and a promoter blocked the repressive effects of the silencer on that promoter at HMR and at telomeres. Sequence analysis indicated that the boundary element contained a TY1 LTR, and a tRNA gene and mutational analysis has implicated the Smc proteins, which encode structural components of chromosomes, in boundary element function.

Genes, Fungal↗

Chromatin assembly: biochemical identities and genetic redundancy.

Investigations on chromatin assembly in vitro implicate chromatin assembly factor 1 (CAF1) as a chaperone for histones H3/H4 and nucleosome assembly protein 1 (NAP1) as a chaperone for histones H2A/H2B. Deletion analysis of CAF1 in vivo suggests multiple redundant pathways for deposition of the histones. Histone deposition requires acetylation of the amino-terminal tails and analysis of mutants suggests a specific but redundant role for acetylation of the tails in assembly. Furthermore, studies on the HAT1 acetyltransferase raise the possibility that acetylation of histones occurs following their transport into the nucleus but prior to their deposition onto DNA. Identification of the factors involved in the redundant pathways of assembly is awaited.

Acetylation↗

Alcohol consumption by nursing rats and its effect on the cerebellum of the offspring.

To study the effect of alcohol on Purkinje cells and on myelination of the cerebellum of neonate rats, female Sprague-Dawley rats were fed alcohol (ethanol) during their nursing period. The alcohol was given in amounts of 5% or 10% per volume of drinking water. Food and liquids, equal in calories, were distributed among dams receiving alcohol. One group of control rats received similar diet but no alcohol. The results were then compared with those of a second group of controls, receiving no alcohol but having access to unlimited supplies of food and water. Histological examination of pups revealed degenerative changes in Purkinje cells and delayed myelination of the cerebellum.

Alcohol Drinking↗

Patterns of organellar and nuclear inheritance among progeny of two geographically isolated strains of Volvox carteri.

Strains of Volvox carteri forma nagariensis derived from Japanese and Indian isolates ("J" and "I" strains, respectively) exhibited length differences (RFLPs) for approximately 90% of the restriction fragments detected by hybridization with a variety of unique-sequence, small-gene-family and repetitive-element probes, including heterologous probes of chloroplast and mitochondrial origin. Extensive post-zygotic mortality was observed among the zygotes produced by crossing J and I strains, suggesting some form of genetic incompatability between them. Most of the viable progeny exhibited recombinant patterns of nuclear inheritance and maternal inheritance of mitochondrial and chloroplast markers. However, many progeny exhibited exclusively uniparental (usually maternal, but in one case paternal) inheritance of both nuclear and organellar markers. Some of these non-recombinant individuals may be derived from "parthenospores" (dormant asexual cells resembling zygospores). Others may be a result of "pseudogamy," in which one of the parental pronuclei is excluded from the zygote, followed by selective exclusion of both the mitochondrial and the chloroplast genomes derived from that same parent. When segregation patterns for 44 nuclear markers were analyzed in 90 recombinant progeny, statistically significant, locus-specific deviations from expected Mendelian transmission ratios were observed for a sizeable fraction of all markers in both reciprocal crosses: some markers were preferentially transmitted by the J strain, while others were preferentially transmitted by the I strain. It is speculated that these transmission distortions may be related to the regions of inter-isolate genetic incompatibility, and may complicate the use of J x I crosses to establish a RFLP-based linkage map for the species.

Animals↗

Beta-lactamase-positive strains of Haemophilus influenzae: susceptibility to and inactivation of beta-lactam antibiotics.

Susceptibility and time-kill studies were done with low and high inocula of both beta-lactamase-positive and -negative strains of Haemophilus influenzae with cefamandole, ampicillin, cefoperazone, mezlocillin, moxalactam, and ceftriaxone. Bioassay was done to test for antibiotic inactivation by beta-lactamase-positive strains. All six antibiotics were highly active against the low inoculum (10(4) to 10(5) colony-forming units/ml) of beta-lactamase-negative strains; ceftriaxone, moxalactam, and cefoperazone were equally active against the same inoculum concentration of beta-lactamase-positive strains. In contrast, cefamandole, mezlocillin, and ampicillin were less active against the low inoculum of beta-lactamase-positive H influenzae. A marked inoculum effect occurred with the high inoculum (10(7) to 10(8) CFU/ml) with all six antibiotics, regardless of beta-lactamase production. In time-kill studies, marked differences in bacterial killing resulted after low and high inocula. Ampicillin, cefamandole, cefoperazone, and mezlocillin were rapidly inactivated by the high inoculum of beta-lactamase-positive H influenzae.

Ampicillin↗

Cardiomyopathy associated with vitamin E deficiency in seven gelada baboons.

Between November 1979 and July 1982, 7 captive gelada baboons (Theropithecus gelada) died; 5 of them died unexpectedly, 1 died after a 4-month history of heart failure, and 1 was anemic and dyspneic for 2 days before death. Of those that died unexpectedly, 1 was anemic and 4 were clinically normal. At necropsy, all baboons had white or pale patches of myocardium. Histologically, fibrosis and acute myocytolysis were observed in the myocardium. Three affected baboons were tested for plasma alpha-tocopherol content and were found deficient. Four unaffected baboons were given vitamin E for 24 months, and plasma alpha-tocopherol content returned to normal. Blood selenium content was determined in 1 affected baboon and was normal.

Anemia↗

Myelopathy and vitamin E deficiency in six Mongolian wild horses.

Degenerative myelopathy was diagnosed in six Mongolian wild horses. Three of the horses had a history of ataxia dating from birth to 3 months of age. The clinical signs were uncoordinated movement of the hindlimbs and an abnormally wide-based gait and stance. The other 3 horses had mild ataxia. There were no gross lesions in the brain, vertebrae, or spinal cord. Histologic examination revealed degeneration of the neural processes in the ventral and lateral funiculi of all 6 horses. Myelin sheaths were dilated and vacuolated, and there were swollen, fragmented, or lysed axons. Neuronal degeneration, phagocytosis, and accumulation of periodic acid-Schiff-positive, xylol-insoluble lipopigment were observed in the affected neurons of the dorsal root ganglia. The plasma alpha-tocopherol values of 5 of the affected horses ranged from less than 0.03 to 0.08 (mean, 0.04 +/- 0.01) mg/dl. Seven clinically normal horses from the same herd had a range of less than 0.03 to 0.3 (mean, 0.11 +/- 0.02) mg/dl, which was low enough to be considered deficient.

Animal Population Groups↗

Mercury intoxication simulating amyotrophic lateral sclerosis.

A 54-year-old man had a syndrome resembling amyotrophic lateral sclerosis after a brief but intense exposure to elemental mercury. The syndrome resolved as his urinary mercury levels fell. Mercury toxicity must be considered not only in individuals with recent anterior horn-cell dysfunction but also with otherwise unexplained peripheral neuropathy, tremor, ataxia, and a gamut of psychiatric symptoms including confusion and depression.

Amyotrophic Lateral Sclerosis↗