Sld5 Ensures Centrosomal Resistance to Congression Forces by Preserving Centriolar Satellites

ABSTRACT

The migration of chromosomes during mitosis is mediated primarily by kinesins that bind to the chromosomes and move along the microtubules, exerting pulling and pushing forces on the centrosomes. We report that a DNA replication protein, Sld5, localizes to the centrosomes, resisting the microtubular pulling forces experienced during chromosome congression. In the absence of Sld5, centriolar satellites, which normally cluster around the centrosomes, are dissipated throughout the cytoplasm, resulting in the loss of their known function of recruiting the centrosomal protein, pericentrin. We observed that Sld5-deficient centrosomes lacking pericentrin were unable to endure the CENP-E- and Kid-mediated microtubular forces that converge on the centrosomes during chromosome congression, resulting in monocentriolar and acentriolar spindle poles. The minus-end-directed kinesin-14 motor protein, HSET, sustains the traction forces that mediate centrosomal fragmentation in Sld5-depleted cells. Thus, we report that a DNA replication protein has an as yet unknown function of ensuring spindle pole resistance to traction forces exerted during chromosome congression.

KEYWORDS:

• GINS
• kinesin CENP-E
• multipolarity
• centriolar satellites
• chromosome congression
• microtubule forces

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at https://doi.org/10.1128/MCB.00371-17.

ACKNOWLEDGMENTS

We thank Ritu Shekhar, Sheetal Uppal, Nasir Imam, and Sunder Bisht for helping with various parts of the manuscript. We thank Daniel Gerlich and Patrick Meraldi for the stable cell lines.

This study was supported by sanctioned projects from DBT and DST, Government of India, and a NET fellowship to M.K.