title: Aurora A Kinase Contributes to a Pole-Based Error Correction Pathway.
abstract: Chromosome biorientation, where sister kinetochores attach to microtubules (MTs) from opposing spindle poles, is the configuration that best ensures equal partitioning of the genome during cell division. Erroneous kinetochore-MT attachments are commonplace but are often corrected prior to anaphase. Error correction, thought to be mediated primarily by the centromere-enriched Aurora B kinase (ABK), typically occurs near spindle poles; however, the relevance of this locale is unclear. Furthermore, polar ejection forces (PEFs), highest near poles, can stabilize improper attachments by pushing mal-oriented chromosome arms away from spindle poles. Hence, there is a conundrum: erroneous kinetochore-MT attachments are weakened where PEFs are most likely to strengthen them. Here, we report that Aurora A kinase (AAK) opposes the stabilizing effect of PEFs. AAK activity contributes to phosphorylation of kinetochore substrates near poles and its inhibition results in chromosome misalignment and an increased incidence of erroneous kinetochore-MT attachments. Furthermore, AAK directly phosphorylates a site in the N-terminal tail of Ndc80/Hec1 that has been implicated in reducing the affinity of the Ndc80 complex for MTs when phosphorylated. We propose that an AAK activity gradient contributes to correcting mal-oriented kinetochore-MT attachments in the vicinity of spindle poles.
authors.affiliation: Biology Department, University of Massachusetts Amherst, Amherst, MA 01003, USA; Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Ye
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, UK.
authors.forename: Jovana
authors.initials: J
authors.lastname: Deretic
authors.affiliation: Biology Department, University of Massachusetts Amherst, Amherst, MA 01003, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hoel
authors.affiliation: Department of Biological Sciences and Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Albert W
authors.initials: AW
authors.lastname: Hinman
authors.affiliation: Department of Biological Sciences and Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimini
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, UK.
authors.forename: Julie P
authors.initials: JP
authors.lastname: Welburn
authors.affiliation: Biology Department, University of Massachusetts Amherst, Amherst, MA 01003, USA; Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA. Electronic address: tmaresca@bio.umass.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Maresca
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D045584:Chromosome Positioning; D059006:Chromosomes, Insect / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; D064096:Aurora Kinase A; C576942:aurA protein, Drosophila