The fission yeast NIMA kinase Fin1p is required for spindle function and nuclear envelope integrity

Abstract

NIMA kinases appear to be the least functionally conserved mitotic regulators, being implicated in chromosome condensation in fungi and in spindle function in metazoans. We demonstrate here that the ®ssion yeast NIMA homologue, Fin1p, can induce profound chromosome condensation in the absence of the condensin and topoisomerase II, indicating that Fin1p-induced condensation differs from mitotic condensation. Fin1p expression is transcriptionally and posttranslationally cell cycle-regulated, with Fin1p kinase activity maximal from the metaphase±anaphase transition to G 1 . Fin1p is localized to the spindle pole body and ®n1D cells are hypersensitive to anti-microtubule drugs, synthetically lethal with a number of spindle mutants and require the spindle checkpoint for viability. Moreover, ®n1D cells show unusual and extensive elaborations of the nuclear envelope. These data support a role for Fin1p in spindle function and nuclear envelope transactions at or after the metaphase± anaphase transition that may be generally applicable to other NIMA-family members.

TINA Interacts with the NIMA Kinase inAspergillus nidulansand Negatively Regulates Astral Microtubules during Metaphase Arrest

“…Additionally, forcing cells into mitosis without normal NIMA activity by mutation of the bimE APC/C component causes marked mitotic defects with SPBs unable to nucleate normal bipolar spindles in the absence of fully active NIMA (Osmani et al, 1991b). Data from other systems also support a role for NIMA-related kinases in spindle formation (Grallert and Hagan, 2002;Krien et al, 2002). The current work indicates a potential role for the NIMA interacting protein TINA in astral microtubule formation during mitosis.…”

“…Although NIMA is essential for mitotic progression in A. nidulans (Ye et al, 1998) the NIMA-like Fin1p kinase of S. pombe is nonessential (Grallert and Hagan, 2002;Krien et al, 1998) but does play a role in mitotic regulation (Krien et al, 2002). Fin1p has therefore been proposed to play a fine-tuning role for mitotic progression and TINA could also be involved in such fine-tuning nonessential mitotic functions.…”

“…Stable versions of NIMA prevent normal exit from mitosis . The mitotic promoting activity of NIMA crosses species barriers from yeast to humans (Lu and Hunter, 1995a), indicating conserved NIMA substrates are involved in mitotic regulation.NIMA-related kinases have been isolated from Neurospora crassa and Schizosaccharomyces pombe (Krien et al, 1998), and the S. pombe NIMA-like kinase Fin1p is involved in mitotic regulation (Grallert and Hagan, 2002;Krien et al, 2002). NIMA-related kinases (NEKs) have also been identified in higher eukaryotes (Letwin et al, 1992;Schultz and Nigg, 1993;Lu and Hunter, 1995b;Chen et al, 1999;Tanaka and Nigg, 1999;Uto and Sagata, 2000;Kandli et al, 2000;Holland et al, 2002;Roig et al, 2002), some of which have been implicated in cell cycle progression.…”

Caught Nek-ing: cilia and centrioles

“…This mechanism of nuclear membrane fission might therefore be specific to this group (Davies et al, 2004). However, a role for NIMA in nuclear membrane fission might be common to all fungi: the kinase activity of the Schizosaccharomyces pombe NIMA ortholog (Fin1p) peaks at the metaphaseanaphase transition, and fin1-deletion mutants have extensive elaborations of the nuclear envelope (Krien et al, 2002). Roles in nuclear envelope fission could represent neofunctionalization of the ancestral Nek within the fungi.…”

“…1A), recruits polo kinase (Plo1) to the spindle pole body (Grallert and Hagan, 2002). However, Fin1p affects the spindle at a later point in the cell cycle, after the metaphase-anaphase transition (Krien et al, 2002). Intriguingly, it binds only to spindle pole bodies that are more than two cell cycles old and appears to regulate the polarity of the septum initiation network (SIN), a conserved mitotic exit network (Grallert et al, 2004;Simanis, 2003).…”