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PLoS One. 2017 May 8;12(5):e0177413. doi: 10.1371/journal.pone.0177413. eCollection 2017.

Expression of human Bcl-xL (Ser49) and (Ser62) mutants in Caenorhabditis elegans causes germline defects and aneuploidy.

Author information

1
Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal (Québec) Canada.
2
Institut du cancer de Montréal, Montréal (Québec) Canada.
3
Département de neurosciences, Université de Montréal, Montréal (Québec) Canada.
4
Département de médecine et Spec. médicales, Université de Montréal, Montréal (Québec) Canada.

Abstract

An interesting feature of Bcl-xL protein is the presence of an unstructured loop domain between α1 and α2 helices, a domain not essential for its anti-apoptotic function and absent in CED-9 protein. Within this domain, Bcl-xL undergoes dynamic phosphorylation and dephosphorylation at Ser49 and Ser62 during G2 and mitosis in human cells. Studies have revealed that when these residues are mutated, cells harbour mitotic defects, including chromosome mis-attachment, lagging, bridging and mis-segregation with, ultimately, chromosome instability and aneuploidy. We undertook genetic experiments in Caenorhabditis elegans to understand the importance of Bcl-xL (Ser49) and (Ser62) in vivo. Transgenic worms carrying single-site S49A, S62A, S49D, S62D and dual site S49/62A mutants were generated and their effects were analyzed in germlines of young adult worms. Worms expressing Bcl-xL variants showed decreased egg-laying and hatching potency, variations in the length of their mitotic regions but not of their transition zones, appearance of chromosomal abnormalities at their diplotene stages, and increased germline apoptosis, with the exception of the S62D variants. Some of these transgenic strains, particularly the Ser to Ala variants, also showed slight modulations of lifespan compared to their controls. In addition, RNAi experiments silencing expression of the various Bcl-xL variants reversed their effects in vivo. Our in vivo observations confirmed the importance of Ser49 and Ser62 within Bcl-xL loop domain in maintaining chromosome stability.

PMID:
28481930
PMCID:
PMC5421811
DOI:
10.1371/journal.pone.0177413
[Indexed for MEDLINE]
Free PMC Article

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