A 180bp deletion at the 5' end of nbs. The deletion eliminates the predicted ATG start codon. However, several in-frame ATG codons are present downstream of the deletion, which may be used (a truncated nbs protein is seen using Western blot analysis in this mutant). Recovered during characterisation of the 'site-specific integrase mediated repeated targeting' (SIRT) method (see FBrf0207169), however, the deletion is outside the region of homology used in the construct used for targeting nbs in this study.
chromosome
Animals hemi- or homozygous for nbsΔ180 are viable and recovered at a Mendelian ratio.
nbsΔ180 animals display mild telomere-capping defects, with 0.3 associations per nbsΔ180 nucleus, compared with the wild-type level of 0.04.
Despite the normal appearance of homozygous or hemizygous nbsΔ180 females, they lay embryos that do not hatch (>10,000 embryos counted), even when mated to wild-type males, indicating maternal effect lethality.
Early nbsΔ180 mutant embryos (those examined before cycle 7) appear to be mostly normal, with nuclei occasionally connected by chromosomal bridges (8%). As the embryos developed, more nuclei appear connected by bridges, and nuclei with abnormal DNA content become abundant. Sister nuclei separation failed in 69 out of 228 mitoses; likely, the result of unresolved chromosome bridges. Some of these polyploid nuclei apparently attempt to divide in the next mitosis, creating multiple-lobed nuclei. Mitotic bridges are observed in 38% of anaphases and telophases. most late-stage nbsΔ180 embryos display large nuclei-free areas, and their interior is filled with abnormally large and highly condensed nuclei. These embryos rarely develop signs of gastrulation. Unresolved telomere associations are the most likely mechanism leading to chromosome bridging. Telomere associations are unequivocally identified in 93.4% of nbsΔ180 embryos. Covalent telomere fusions are abundant in nbsΔ180 mutant embryos.
Contrary to the severe capping defect in the embryos, nbsΔ180 postembryonic animals develop mild telomere dysfunction, and are viable.
nbs2K has abnormal mitotic cell cycle phenotype, enhanceable by mre1158S
nbs2K is an enhancer of abnormal mitotic cell cycle phenotype of mre1158S
mre1158S, nbs2K has lethal | pupal stage phenotype
