6 research outputs found
The Complete Genome Sequence of Fibrobacter succinogenes S85 Reveals a Cellulolytic and Metabolic Specialist
Fibrobacter succinogenes is an important member of the rumen
microbial community that converts plant biomass into nutrients usable by its
host. This bacterium, which is also one of only two cultivated species in its
phylum, is an efficient and prolific degrader of cellulose. Specifically, it has
a particularly high activity against crystalline cellulose that requires close
physical contact with this substrate. However, unlike other known cellulolytic
microbes, it does not degrade cellulose using a cellulosome or by producing high
extracellular titers of cellulase enzymes. To better understand the biology of
F. succinogenes, we sequenced the genome of the type strain
S85 to completion. A total of 3,085 open reading frames were predicted from its
3.84 Mbp genome. Analysis of sequences predicted to encode for
carbohydrate-degrading enzymes revealed an unusually high number of genes that
were classified into 49 different families of glycoside hydrolases, carbohydrate
binding modules (CBMs), carbohydrate esterases, and polysaccharide lyases. Of
the 31 identified cellulases, none contain CBMs in families 1, 2, and 3,
typically associated with crystalline cellulose degradation. Polysaccharide
hydrolysis and utilization assays showed that F. succinogenes
was able to hydrolyze a number of polysaccharides, but could only utilize the
hydrolytic products of cellulose. This suggests that F.
succinogenes uses its array of hemicellulose-degrading enzymes to
remove hemicelluloses to gain access to cellulose. This is reflected in its
genome, as F. succinogenes lacks many of the genes necessary to
transport and metabolize the hydrolytic products of non-cellulose
polysaccharides. The F. succinogenes genome reveals a bacterium
that specializes in cellulose as its sole energy source, and provides insight
into a novel strategy for cellulose degradation
Modulation of the cancer susceptibility measure, adenosine diphosphate ribosyl transferase (ADPRT), by differences in lowβdose nβ3 and nβ6 fatty acids
Mechanism of aortic medial matrix remodeling is distinct in patients with bicuspid aortic valve
Unique tissue-specific level of DNA nucleotide excision repair in primary human mammary epithelial cultures
DNA repair is essential for the maintenance of genomic integrity and stability. Nucleotide excision repair (NER) is a major pathway responsible for remediation of damage caused by UV light, bulky adducts, and cross-linking agents. We now show that NER capacity is differentially expressed in human tissues. We established primary cultures of peripheral blood lymphocytes (PBLs: N = 33) and foreskin fibroblasts (FF: N = 6), as well as adult breast tissue (N = 22) using a unique culture system, and measured their NER capacity using the unscheduled DNA synthesis (UDS) functional assay. Relative to FF, primary cultures of breast cells exhibited only 24.6 +/- 2.1% of NER capacity and PBLs only 8.9 +/- 1.2%. Cells from the breast therefore have a unique and distinctive DNA repair capacity. The NER capacities of all three cell types had similar coefficients of variation in the range of 10%-15%, which should be taken into account when running controls for this contextual assay. Unlike previous studies and speculation in the field, we found that NER was not affected by cell morphology, donor age, or proliferation as measured by the S phase index. While the NER capacity of the transformed lymphoblastoid cell line TK6 was within the range of our PBL samples, the breast tumor-derived MDA MB-231 cell line was four-fold higher than normal breast tissue. These studies show that analysis of baseline DNA repair in normal human cell types is critical as a basis for evaluation of the effects of mutator genes as etiological factors in the development of cancer