Genetic Analysis Of A sas‐6 Mutant Reveals Mitotic and Meiotic Differences In Centriole Duplication Stability

Abstract

Centrioles are nine‐fold symmetric barrel‐shaped organelles that exist as mother‐daughter pairs that participate in the assembly of bipolar spindles and the formation of cilia and flagella. During S phase of each cell cycle, centrioles are precisely duplicated through a process that involves the formation of a new daughter next to each preexisting mother centriole. In Caenorhabditis elegans, as in other species including humans, five core centriole assembly factors are required for centriole duplication and these same factors function in different cell types, suggesting that a similar assembly mechanism operates in all tissues. SAS‐6 is one of these core assembly factors and plays a critical role in centriole assembly by forming a central scaffold around which the daughter is built. Here we describe a missense (D9V) mutation in C. elegans SAS‐6 that strongly affects the formation and/or stability of centrioles in the meiotic portion of the male germ line and continues to effect centriole formation and/or stability in the mitotic environment of the early embryo. Examination of mutant male germ lines indicates that both the incorporation of SAS‐6(D9V) into daughter centrioles and centriole assembly occur during pre‐meiotic centriole duplication. However, during meiosis daughter centrioles fail to form and SAS‐6(D9V) is gradually lost from most of the mother centrioles. As a result, sperm inherit a single structurally‐disorganized centriole that further deteriorates after it is transferred to an embryo at fertilization. These structurally deficient centrioles lead to inconsistent duplication in the embryo with wild type maternal sas‐6 as evidenced by monopolar spindle formation. This is consistent with evidence in the literature that the mother centriole plays a role in the structural formation of the daughter centriole. Thus, the D9V mutation preferentially affects centriole stability and duplication during meiotic divisions and continues to this instability into the mitotic divisions. Further genetic and cytological analysis of this mutant will allow us to identify whether the mother centriole does more than recruit required proteins but also provides a structural template in daughter centriole formation.Support or Funding InformationIntramural funding from NIDDK, NIHThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.