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Sensitive Mutant (sensitive + mutant)

Distribution by Scientific Domains

Life Sciences	60%

Selected Abstracts

Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repair

GENES TO CELLS, Issue 9 2001
Jun Morishita
Background In mammals, proteins containing BIR domains (IAPs and survivin) are implicated in inhibiting apoptosis and sister chromatid separation. In the nematode, Bir1 is required for a proper localization of aurora kinase, which moves from the mitotic chromosome in metaphase to the spindle midzone in anaphase as a passenger. Fission yeast Bir1/Pbh1 is essential for normal mitosis. Results A temperature sensitive mutant cut17-275 exhibits the defect in condensation and spindle elongation at 36 °C, while securin is degraded. Gene cloning shows that the cut17+ gene is identical to bir1+/pbh1+. At 26 °C, cut17-275 is UV sensitive as the repair of DNA damage is severely compromised. Bir1/Cut17 is a nuclear protein in interphase, which is then required for recruiting condensin to the mitotic nucleus, and concentrates to form a discrete number of dots from prometaphase to metaphase. Once the chromatids are separated, Bir1/Cut17 no longer binds to kinetochores and instead moves to the middle of spindle. Chromatin immunoprecipitation suggested that Bir1/Cut17 associates with the outer repetitious centromere region in metaphase. Following the initiation of anaphase the protein switches from being a chromosomal protein to a spindle protein. This transit is stringently regulated by the state of sister chromatid cohesion proteins Mis4 and Rad21. Ark1, is an aurora kinase homologue whose mitotic distribution is identical to, and under the control of Bir1/Cut17. Conclusions Bir1/Cut17 and Ark1 act as ,passengers' but they may play a main role as a recruitment factor, essential for condensation, spindle elongation and DNA repair. Bir1/Cut17 should have roles both in mitotic and in interphase chromosome. The proper location of Ark1 requires Bir1/Cut17, and the mitotic localization of Bir1/Cut17 requires sister cohesion. [source]

Mis3 with a conserved RNA binding motif is essential for ribosome biogenesis and implicated in the start of cell growth and S phase checkpoint

GENES TO CELLS, Issue 7 2000
Hiroshi Kondoh
Background In normal somatic cell cycle, growth and cell cycle are properly coupled. Although CDK (cyclin-dependent kinase) activity is known to be essential for cell cycle control, the mechanism to ensure the coupling has been little understood. Results We here show that fission yeast Mis3, a novel evolutionarily highly conserved protein with the RNA-interacting KH motif, is essential for ribosome RNA processing, and implicated in initiating the cell growth. Growth arrest of mis3-224, a temperature sensitive mutant at the restrictive temperature, coincides with the early G2 block in the complete medium or the G1/S block in the release from nitrogen starvation, reflecting coupling of cell growth and division. Genetic interactions indicated that Mis3 shares functions with cell cycle regulators and RNA processing proteins, and is under the control of Dsk1 kinase and PP1 phosphatase. Mis3 is needed for the formation of 18S ribosome RNA, and may hence direct the level of proteins required for the coupling. One such candidate is Mik1 kinase. mis3-224 is sensitive to hydroxyurea, and the level of Mik1 protein increases during replication checkpoint in a manner dependent upon the presence of Mis3 and Cds1. Conclusions Mis3 is essential for ribosome biogenesis, supports S phase checkpoint, and is needed for the coupling between growth and cell cycle. Whether Mis3 interacts solely with ribosomal precursor RNA remains to be determined. [source]

Biochemical properties of the cell wall in the Arabidopsis mutant bor1-1 in relation to boron nutrition

JOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 2 2003
Kyotaro Noguchi
Abstract We examined concentrations of boron (B) and dimerization of rhamnogalacturonan II (RG-II), a B-binding polysaccharide, in the cell wall of a low-B sensitive mutant of Arabidopsis thaliana, bor1-1, to investigate possible effects of the bor1-1 mutation on the biochemical form of pectins in the cell wall. In the bor1-1 mutant, B concentrations in the cell wall from shoots were lower than those in the wild type at low B supply, whereas they were similar at sufficient B supply. The amount of B present as borate ester of the RG-II dimer (dRG-II-B) in the bor1-1 mutant was lower than that in the wild type at low B supply. In the wild type, about 90,% of RG-II was present as dRG-II-B, both, at low and sufficient B supply. In the bor1-1 mutant, about 60,% of RG-II was in its monomeric form (mRG-II) at low B supply, whereas more than 85,% of it was present as dRG-II-B at sufficient B supply. However, similar as the wild type, mRG-II derived from the bor1-1 mutant was able to form dRG-II-B in vitro in the presence of borate and lead. Sugar composition of cell wall fractions was similar in both genotypes. These results suggest that the polysaccharide composition in the cell wall was not strongly affected by the bor1-1 mutation. The observed difference in dimerization of RG-II at low B supply is most likely due to a reduced B concentration in the shoots of the bor1-1 mutant. Biochemische Eigenschaften der Zellwände der Arabidopsis -Mutante bor1-1 bei unterschiedlicher Borernährung Um die Auswirkungen der bor1-1 -Mutation auf die biochemische Beschaffenheit von Zellwandpektinen zu verstehen, haben wir den Bor(B) -Gehalt und den Status des B-bindenden Polysaccharids Rhamnogalacturonan-II (RG-II) in den Zellwänden einer Arabidopsis thaliana -Mutante (bor1-1) untersucht. Diese Mutante reagiert empfindlich auf niedriges Borangebot. Bei niedriger Borversorgung waren die Borgehalte in der Zellwand des Sprosses der bor1-1 -Mutante niedriger als die des Wildtyps. Dagegen lagen die Borgehalte der bor1-1 -Mutante und des Wildtyps bei guter Borversorgung in einem ähnlichen Bereich. Der Boranteil, der im RG-II-Dimer (dRG-II-B) als Borester vorlag, war bei niedriger Borversorgung in der bor1-1 -Mutante geringer als im Wildtyp. Im Wildtyp lagen sowohl bei niedriger als auch bei hoher Borversorgung 90,% des RG-II als dRG-II-B vor. In der bor1-1- Mutante lagen dagegen bei niedriger Borversorgung 60,% des RG-II in monomerer Form (mRG-II) vor, während bei guter Borversorgung der Anteil von dRG-II-B 85,% ausmachte. Allerdings war mRG-II, das aus der bor1-1 -Mutante gewonnen wurde, fähig, in gleicher Weise wie beim Wildtyp in der Gegenwart von Borat und Bleiionen in vitro dRG-II-B zu bilden. Die Zuckerzusammensetzung der Zellwandfraktionen war in beiden Genotypen ähnlich. Diese Ergebnisse lassen vermuten, dass die Polysaccharidzusammensetzung in der Zellwand nicht gravierend von der bor1-1 -Mutation beeinflusst wurde. Der beobachtete Unterschied in der Dimerisierung von RG-II bei niedriger Borversorgung beruht wahrscheinlich auf dem geringeren Borgehalt im Spross der bor1-1 -Mutante. [source]

Nitric oxide modulates ozone-induced cell death, hormone biosynthesis and gene expression in Arabidopsis thaliana

THE PLANT JOURNAL, Issue 1 2009
Reetta Ahlfors
Summary Nitric oxide (NO) is involved together with reactive oxygen species (ROS) in the activation of various stress responses in plants. We have used ozone (O3) as a tool to elicit ROS-activated stress responses, and to activate cell death in plant leaves. Here, we have investigated the roles and interactions of ROS and NO in the induction and regulation of O3 -induced cell death. Treatment with O3 induced a rapid accumulation of NO, which started from guard cells, spread to adjacent epidermal cells and eventually moved to mesophyll cells. During the later time points, NO production coincided with the formation of hypersensitive response (HR)-like lesions. The NO donor sodium nitroprusside (SNP) and O3 individually induced a large set of defence-related genes; however, in a combined treatment SNP attenuated the O3 induction of salicylic acid (SA) biosynthesis and other defence-related genes. Consistent with this, SNP treatment also decreased O3 -induced SA accumulation. The O3 -sensitive mutant rcd1 was found to be an NO overproducer; in contrast, Atnoa1/rif1 (Arabidopsis nitric oxide associated 1/resistant to inhibition by FSM1), a mutant with decreased production of NO, was also O3 sensitive. This, together with experiments combining O3 and the NO donor SNP suggested that NO can modify signalling, hormone biosynthesis and gene expression in plants during O3 exposure, and that a functional NO production is needed for a proper O3 response. In summary, NO is an important signalling molecule in the response to O3. [source]

DNA ligase IV is a potential molecular target in ACNU sensitivity

CANCER SCIENCE, Issue 8 2010
Natsuko Kondo
Nimustine (ACNU) is a chloroethylating agent which was the most active chemotherapy agent used for patients with high-grade gliomas until the introduction of temozolomide, which became the standard of care for patients with newly diagnosed glioblastomas in Japan. Since temozolomide was established as the standard first-line therapy for glioblastoma multiforme (GBM), ACNU has been employed as a salvage chemotherapy agent for recurrent GBM in combination with other drugs. The acting molecular mechanism in ACNU has yet to be elucidated. ACNU is a cross-linking agent which induces DNA double-strand breaks (DSBs). The work described here was intended to clarify details in repair pathways which are active in the repair of DNA DSBs induced by ACNU. DSBs are repaired through the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. Cultured mouse embryonic fibroblasts were used which have deficiencies in DNA DSB repair genes which are involved in HR repair (X-ray repair cross-complementing group 2 [XRCC2] and radiation sensitive mutant 54 [Rad54]), and in NHEJ repair (DNA ligase IV [Lig4]). Cellular sensitivity to ACNU treatment was evaluated with colony forming assays. The most effective molecular target which correlated with ACNU cell sensitivity was Lig4. In addition, it was found that Lig4 small-interference RNA (siRNA) efficiently enhanced cell lethality which was induced by ACNU in human glioblastoma A172 cells. These findings suggest that the down-regulation of Lig4 might provide a useful tool which can be used to increase cell sensitivity in response to ACNU chemotherapy. (Cancer Sci 2010) [source]