De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly

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Abstract

Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.

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Won-Jing Wang

Institute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang-Ming University, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Devrim Acehan

Electron Microscopy Resource Center, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Chien-Han Kao

Institute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang-Ming University, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Wann-Neng Jane

Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Kunihiro Uryu

Electron Microscopy Resource Center, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Meng-Fu (Bryan) Tsou

Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, United States

For correspondence
tsoum@mskcc.org

Competing interests
The authors declare that no competing interests exist.

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