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R Heald

Publications and source records attributed to R Heald.

23 records · Page 2Linked to original sources
PubMed1990

Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis.

The nuclear envelope is a dynamic structure that completely disassembles in response to MPF/cdc2 activity in mitosis. A key feature of this process is the hyperphosphorylation of the major structural proteins of the envelope, the nuclear lamins A, B, and C. Two highly conserved serine residues of the lamin protein (Ser-22 and Ser-392 of lamins A and C) are symmetrically positioned 5 amino acids from the ends of the large alpha-helical domain and are shown in the accompanying paper by Ward and Kirschner to be among four sites phosphorylated during nuclear envelope breakdown. Mutations in Ser-22 and Ser-392 that prevent phosphorylation at these sites block the disassembly of the nuclear lamina during mitosis. We propose a model for the regulation of lamin assembly in which phosphorylation just outside the ends of the alpha-helical domain controls the assembly dynamics of the lamin coiled-coil dimers.

Amino Acid Sequence↗
PubMedDate not supplied

Anastomotic leakage after colorectal anastomosis.

Leakage is a problem largely confined to anastomoses within 6 cm of the anal verge when optimal surgical technique is exercised. At such low levels, most surgeons now use a combination of linear and circular staplers. The Moran Triple Stapling Technique is our chosen method. Most recently, the simultaneous use of two linear staplers to seal the specimen and wash the distal stump is a rapid technique for anastomosis onto the dentate line within the external sphincter. Proximal defunctioning and the short colon pouch with side-to-end colo-anal anastomosis are currently considered optimal. A trial is under way to assess a silastic transanal stent as an alternative. Ultra-low anastomosis, however, remains potentially hazardous and still should be undertaken only by specialists.

Anastomosis, Surgical↗
PubMedDate not supplied

A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity.

BACKGROUND: In eukaryotes, assembly of the mitotic spindle requires the interaction of chromosomes with microtubules. During this process, several motor proteins that move along microtubules promote formation of a bipolar microtubule array, but the precise mechanism is unclear. In order to examine the roles of different motor proteins in building a bipolar spindle, we have used a simplified system in which spindles assemble around beads coated with plasmid DNA and incubated in extracts from Xenopus eggs. Using this system, we can study spindle assembly in the absence of paired cues, such as centrosomes and kinetochores, whose microtubule-organizing properties might mask the action of motor proteins. RESULTS: We blocked the function of individual motor proteins in the Xenopus extracts using specific antibodies. Inhibition of Xenopus kinesin-like protein 1 (Xklp1) led either to the dissociation of chromatin beads from microtubule arrays, or to collapsed microtubule bundles on beads. Inhibition of Eg5 resulted in monopolar microtubule arrays emanating from chromatin beads. Addition of antibodies against dynein inhibited the focusing of microtubule ends into spindle poles in a dose-dependent manner. Inhibition of Xenopus carboxy-terminal kinesin 2 (XCTK2) affected both pole formation and spindle stability. Co-inhibition of XCTK2 and dynein dramatically increased the severity of spindle pole defects. Inhibition of Xklp2 caused only minor spindle pole defects. CONCLUSIONS: Multiple microtubule-based motor activities are required for the bipolar organization of microtubules around chromatin beads, and we propose a model for the roles of the individual motor proteins in this process.

Animals↗