By comparing 195 varieties in eight trials, this study assesses nitrogen use efficiency improvement in high and low nitrogen conditions in European winter wheat over the last 25 years. In a context where European agriculture practices have to deal with environmental concerns and nitrogen (N) fertiliser cost, nitrogen use efficiency (NUE) has to be improved. This study assessed genetic progress in winter wheat (Triticum aestivum L.) NUE. Two hundred and twenty-five European elite varieties were tested in four environments under two levels of N. Global genetic progress was assessed on additive genetic values and on genotype × N interaction, covering 25 years of European breeding. To avoid sampling bias, quality, precocity and plant height were added as covariates in the analyses when needed. Genotype × environment interactions were highly significant for all the traits studied to such an extent that no additive genetic effect was detected on N uptake. Genotype × N interactions were significant for yield, grain protein content (GPC), N concentration in straw, N utilisation, and NUE. Grain yield improvement (+0.45 % year(-1)) was independent of the N treatment. GPC was stable, thus grain nitrogen yield was improved (+0.39 % year(-1)). Genetic progress on N harvest index (+0.12 % year(-1)) and on N concentration in straw (-0.52 % year(-1)) possibly revealed improvement in N remobilisation. There has been an improvement of NUE additive genetic value (+0.33 % year(-1)) linked to better N utilisation (+0.20 % year(-1)). Improved yield stability was detected as a significant improvement of NUE in low compared to high N conditions. The application of these results to breeding programs is discussed.

We have developed ribozymes (Rz) that inhibit BRCA1 expression in order to study the role of this gene in chemosensitivity. Two Rz, targeting positions 358 or 5282 of the BRCA1 mRNA, were cloned into the retroviral vector LXSN and lipofected into the breast cancer cell-line HBL100. We obtained 79 ± 99% inhibition of BRCA1 expression, as determined by real-time quantitative PCR and by Western blotting. Decreased expression of BRCA1 led to sensitivity to the DNA damaging agents cisplatin and etoposide, resistance to the microtubule-interfering agents (MIA) taxol and vincristine. The molecular mechanism of resistance to MIA was investigated further by determining the status of the JNK pathway. We found that JNK1 expression was elevated, while JNK2 expression was decreased in Rz-expressing clones compared to controls. We have quanti®ed the mRNA levels of BRCA1, JNK1, 2, MEK-4, -7 and c-jun after treatment with MIA. Vincristine treatment of control cells resulted in transcriptional repression of BRCA1, while the JNK1, 2, MEK-4, -7 and c-jun genes were induced. In Rz-treated cells, only JNK1 and MEK-4 were expressed and none was induced after MIA treatment. We then studied the phosphorylation of c-jun, a downstream eector of the JNK pathway. We observed a strong increase in phosphorylated c-jun after MIA treatment of the control cells but not in BRCA1-Rz treated cells, suggesting inhibition of the JNK pathway. These results show that the BRCA1-JNK pathway is involved in the cytotoxic response to MIA treatment, and inhibition of BRCA1 leads to transcriptional modi®cations of the JNK pathway. Oncogene (2001) 20, 6597 ± 6606.

). † These authors contributed equally to the work. SUMMARYMonitoring nitrogen use efficiency (NUE) in plants is becoming essential to maintain yield while reducing fertilizer usage. Optimized NUE application in major crops is essential for long-term sustainability of agriculture production. Here, we report the precise identification of 11 major chromosomal regions controlling NUE in wheat that co-localise with key developmental genes such as Ppd (photoperiod sensitivity), Vrn (vernalization requirement), Rht (reduced height) and can be considered as robust markers from a molecular breeding perspective. Physical mapping, sequencing, annotation and candidate gene validation of an NUE metaQTL on wheat chromosome 3B allowed us to propose that a glutamate synthase (GoGAT) gene that is conserved structurally and functionally at orthologous positions in rice, sorghum and maize genomes may contribute to NUE in wheat and other cereals. We propose an evolutionary model for the NUE locus in cereals from a common ancestral region, involving species specific shuffling events such as gene deletion, inversion, transposition and the invasion of repetitive elements.

hBRCA1 is involved in 20-45% of inherited breast cancer cases and is implicated in many mechanisms involved in response to DNA damage. To date, BRCA1 orthologs have been characterized in vertebrate genomes only. We have identified the ortholog of BRCA1 in Arabidopsis thaliana. AtBRCA1 is a 5.5 kb part of the locus At4g21070. The corresponding mRNA of 3.5 kb is composed of 14 exons and encodes a 941 amino acid protein (104 kDa). AtBRCA1, which has one N-terminal RING finger, two C-terminal BRCT and the p300/CBP interacting domain, shows a high similarity to hBRCA1 in these motifs and has the same characteristic molecular organization. We have also identified a putative ortholog in rice (OsBRCA1). With 941 and 968 amino acids, respectively, AtBRCA1 and OsBRCA1 are the shortest members of the BRCA1 family, and may represent a plant specificity. AtBRCA1 is expressed ubiquitously in plant tissues, at levels depending on organ type, with highest levels in flower buds and exponentially growing cell cultures. Increase of mRNA levels in all plant tissues 1 h after irradiation with the highest induction level of approximately 150 times for a 100 Gy dose is consistent with a putative role of AtBRCA1 in DNA repair and in cell-cycle control.