Mps1 kinase promotes sister-kinetochore bi-orientation by a tension-dependent mechanism

TY - JOUR

T1 - Mps1 kinase promotes sister-kinetochore bi-orientation by a tension-dependent mechanism

AU - Maure, Jean-Francois

AU - Kitamura, Etsushi

AU - Tanaka, Tomoyuki U.

PY - 2007/12/18

Y1 - 2007/12/18

N2 - Segregation of sister chromatids to opposite spindle poles during anaphase is dependent on the prior capture of sister kinetochores by microtubules extending from opposite spindle poles (bi-orientation). If sister kinetochores attach to microtubules from the same pole (syntelic attachment), the kinetochore-spindle pole connections must be re-oriented to be converted to proper bi-orientation [1, 2]. This re-orientation is facilitated by Aurora B kinase (IpI1 in budding yeast), which eliminates kinetochore-spindle pole connections that do not generate tension [3-6]. Mps1 is another evolutionarily conserved protein kinase, required for spindle-assembly checkpoint and, in some organisms, for duplication of microtubule-organizing centers [7]. Separately from these functions, however, Mps1 has an important role in chromosome segregation [8]. Here we show that, in budding yeast, Mps1 has a crucial role in establishing sister-kinetochore bi-orientation on the mitotic spindle. Failure in bi-orientation with inactive Mps1 is not due to a lack of kinetochore-spindle pole connections by microtubules, but due to a defect in properly orienting the connections. Mps1 promotes re-orientation of kinetochore-spindle pole connections and eliminates those that do not generate tension between sister kinetochores. We did not find evidence that IpI1 regulates Mps1 or vice versa; therefore, they play similar, but possibly independent, roles in facilitating bi-orientation.

AB - Segregation of sister chromatids to opposite spindle poles during anaphase is dependent on the prior capture of sister kinetochores by microtubules extending from opposite spindle poles (bi-orientation). If sister kinetochores attach to microtubules from the same pole (syntelic attachment), the kinetochore-spindle pole connections must be re-oriented to be converted to proper bi-orientation [1, 2]. This re-orientation is facilitated by Aurora B kinase (IpI1 in budding yeast), which eliminates kinetochore-spindle pole connections that do not generate tension [3-6]. Mps1 is another evolutionarily conserved protein kinase, required for spindle-assembly checkpoint and, in some organisms, for duplication of microtubule-organizing centers [7]. Separately from these functions, however, Mps1 has an important role in chromosome segregation [8]. Here we show that, in budding yeast, Mps1 has a crucial role in establishing sister-kinetochore bi-orientation on the mitotic spindle. Failure in bi-orientation with inactive Mps1 is not due to a lack of kinetochore-spindle pole connections by microtubules, but due to a defect in properly orienting the connections. Mps1 promotes re-orientation of kinetochore-spindle pole connections and eliminates those that do not generate tension between sister kinetochores. We did not find evidence that IpI1 regulates Mps1 or vice versa; therefore, they play similar, but possibly independent, roles in facilitating bi-orientation.

KW - SPINDLE-ASSEMBLY CHECKPOINT

KW - BUDDING YEAST

KW - PROTEIN-KINASE

KW - PRECOCIOUS SEPARATION

KW - MOLECULAR-MECHANISMS

KW - MITOTIC SPINDLE

KW - CHROMOSOME

KW - ATTACHMENT

KW - REVEALS

KW - MITOSIS

U2 - 10.1016/j.cub.2007.11.032

DO - 10.1016/j.cub.2007.11.032

M3 - Article

C2 - 18060784

SN - 0960-9822

VL - 17

SP - 2175

EP - 2182

JO - Current Biology

JF - Current Biology

IS - 24

ER -