The centriolar satellite protein Cep131 is important for genome stability.
The centrosome acts as a centre for microtubule organisation and plays crucial roles in cell polarity, migration, growth and division. Cep131 has recently been described as a basal body component essential for cilium formation, but its function in non-ciliogenic cells is unknown. We identified human Cep131 (also known as AZI1) in a screen for regulators of genome stability. We show that centrosomal localisation of Cep131 is cell-cycle-regulated and requires both an intact microtubule network and a functional dynein-dynactin transport system. Cep131 is recruited to centriolar satellites by PCM1, and localised to the centriolar core region by both pericentrin and Cep290. Depletion of Cep131 results in a reduction in proliferation rate, centriole amplification, an increased frequency of multipolar mitosis, chromosomal instability and an increase in post-mitotic DNA damage. These data therefore highlight the importance of human Cep131 for maintaining genomic integrity.
Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, YCR Institute for Cancer Studies, Department of Oncology, University of Sheffield Medical School, UK.
Christopher J
CJ
Staples
Katie N
KN
Myers
Ryan D D
RD
Beveridge
Abhijit A
AA
Patil
Alvin J X
AJ
Lee
Charles
C
Swanton
Michael
M
Howell
Simon J
SJ
Boulton
Spencer J
SJ
Collis
D000951:Antigens, Neoplasm / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000235:genetics / Q000648:ultrastructure; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D043171:Chromosomal Instability; D003598:Cytoskeletal Proteins; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism
D000951:Antigens, Neoplasm; D001324:Autoantigens; C578334:CEP131 protein, human; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D000072159:Dynactin Complex; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C086074:PCM1 protein, human; D004398:Dyneins