Effect of DNA base composition on the intercalation of proflavine. A kinetic study.

The effect of DNA base composition on the kinetics of the association between DNA and proflavine has been investigated using the temperature jump relaxation method. It is found that, regardless of the G + C base composition the results fit a two step mechanism, the second of which exhibits characteristics of intercalation of proflavine into DNA. However, they two equilibrium constants corresponding to these steps, KI and KII, depend on the nature of the DNAs. The constant KI is found to be an order of magnitude greater for M. lysodeikticus DNA (72% G + C) than for calf thymus DNA (48% G + C). Increasing G-C content thus appears to favor the intermediate non-intercalated complex of proflavine with DNA. Methylation of M. lysodeikticus DNA with dimethyl sulfate, preferentially yielding N7 methyl guanine as the modified base, again leads to an apparent two step mechanism, with the value of KI unchanged with respect to untreated DNA, while the affinity of proflavine for the intercalated complex measured by the value of KII increases for methylated DNA.     

S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex

Double-strand breaks (DSBs) in chromosomes are the most challenging type of DNA damage. The yeast and mammalian Mre11-Rad50-Xrs2/Nbs1 (MRX/N)-Sae2/Ctp1 complex catalyzes the resection of DSBs induced by secondary structures, chemical adducts or covalently-attached proteins. MRX/N also initiates two parallel DNA damage responses—checkpoint phosphorylation and global SUMOylation—to boost a cell''s ability to repair DSBs. However, the molecular mechanism of this SUMO-mediated response is not completely known. In this study, we report that Saccharomyces cerevisiae Mre11 can non-covalently recruit the conjugated SUMO moieties, particularly the poly-SUMO chain. Mre11 has two evolutionarily-conserved SUMO-interacting motifs, Mre11^SIM1 and Mre11^SIM2, which reside on the outermost surface of Mre11. Mre11^SIM1 is indispensable for MRX assembly. Mre11^SIM2 non-covalently links MRX with the SUMO enzymes (E2/Ubc9 and E3/Siz2) to promote global SUMOylation of DNA repair proteins. Mre11^SIM2 acts independently of checkpoint phosphorylation. During meiosis, the mre11^SIM2 mutant, as for mre11S, rad50S and sae2Δ, allows initiation but not processing of Spo11-induced DSBs. Using MRX and DSB repair as a model, our work reveals a general principle in which the conjugated SUMO moieties non-covalently facilitate the assembly and functions of multi-subunit protein complexes.     

Reactivity of anti nucleoside antibodies with metaphase chromosomes.

It is shown that the binding of anti-nucleoside antibodies to fixed human metaphase chromosomes can be revealed using the immunoperoxidase procedure while under the same conditions no antibody binding is revealed using the immunofluorescence procedure.     

Requirement of lipocalin 2 for hematopoietic and solid tumor malignancies

Our published studies indicate that lipocalin 2 is a critical factor for invasion of hematopoietic tissues by chronic myelogenous leukemia cells. Lipocalin 2 is secreted by Bcr-Abl+ chronic myeloid leukemia cells causing apoptosis in normal hematopoietic cells but not in Bcr-Abl+ cells. Secreted lipocalin 2 forms a complex with metalloproteinase MMP-9, and is reported to stabilize its activity, which implies that lipocalin 2 may have a role in solid tumor formation. Our studies indicate that Bcr-Abl+ mouse marrow cells lacking the lipocalin 2 gene are not only defective for leukemia induction but also are defective in forming solid tumors compared to Bcr-Abl marrow cells that express lipocalin 2. Thus, our findings indicate that lipocalin 2 has two functions in tumor malignancies: one involving induction of apoptosis in normal hematopoietic cells and the other to facilitate solid tumor formation.     

METTL9 mediated N1-histidine methylation of zinc transporters is required for tumor growth

Dear Editor, Histidine methylation has been known for many years(Searle and Westall,1951),but only a few proteins carrying such modifications have been studied ...     

MiR-718 represses VEGF and inhibits ovarian cancer cell progression

Oncogenic activation of VEGF is found in various malignancies, including ovarian cancer. In this study, we investigate the role of microRNA (miRNA) in the regulation of VEGF in ovarian cancer. We find that miR-718 is expressed at low levels and inversely correlates with VEGF expression in ovarian cancer specimens. MiR-718 also directly targets and represses VEGF expression. In addition, miR-718 restoration inhibits ovarian cancer proliferation both in vitro and in vivo. Moreover, VEGF expression could reverse the effect of miR-718 on ovarian cancer by increasing the levels of phosphorylated AKT. These results suggest a new therapeutic strategy in ovarian cancer by restoring miR-718 expression, which is involved in VEGF regulation.     

Identification of candidate genes related to highland adaptation from multiple Chinese local chicken breeds by whole genome sequencing analysis

Understanding the genetic mechanism of highland adaptation is of great importance for breeding improvement of Tibetan chickens (TBC). Some studies of TBC have identified some candidate genes and pathways from multiple subgroups, but the related genetic mechanisms remain largely unknown. Different genetic backgrounds and the independent genetic basis of highland adaptation make it difficult to identity the selective region of highland adaptation with all TBC samples. In this study, we conducted pre-analysis in a large-scale population to select a TBC subgroup with the purest and highest level of highland-specific lineage for the further analysis. Finally, the 37 samples from a TBC subgroup and 19 Lahsa White chickens were used to represent the highland group for further analysis with 80 samples from five Chinese local lowland breeds as controls. Population structure analysis revealed that highland adaptation significantly affected population stratification in Chinese local chicken breeds. Genome-wide selection signal analysis identified 201 candidate genes associated with highland adaptation of TBC, and these genes were significantly enriched in calcium signaling, vascular smooth muscle contraction and the cellular response to oxidative stress pathways. Additionally, we identified a narrow 1.76 kb region containing an overlapping region between HBZ and an active enhancer, and our identified region showed a highly significant signal. The highland group selected the haplotype with high activity to improve the oxygen-carrying capacity, thus being adapted to a hypoxic environment. We also found that STX2 was significantly selected in the highland group, thus potentially reducing the oxidative stress caused by hypoxia, and that STX2 exhibited the opposite effects on highland adaptation and reproductive traits. Our findings advance our understanding of extreme environment adaptation of highland chickens, and provide some variants and genes beneficial to TBC genetic breeding improvement.