Phosphorylation of SAF-A/hnRNP-U Serine 59 by polo-like kinase 1 is required for mitosis

Douglas, P., Ye, R., Morrice, N., Britton, S., Trinkle-Mulcahy, L. and Lees-Miller, S.P. (2015) Phosphorylation of SAF-A/hnRNP-U Serine 59 by polo-like kinase 1 is required for mitosis. Molecular and Cellular Biology, 35(15), pp. 2699-2713. (doi: 10.1128/MCB.01312-14) (PMID:25986610)

Abstract

Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Morrice, Dr Nicholas
• Authors: Douglas, P., Ye, R., Morrice, N., Britton, S., Trinkle-Mulcahy, L., and Lees-Miller, S.P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular and Cellular Biology
• Publisher: American Society for Microbiology
• ISSN: 0270-7306
• ISSN (Online): 1098-5549