RRC ID 46205
Author Stevens D, Oegema K, Desai A.
Title Meiotic double-strand breaks uncover and protect against mitotic errors in the C. elegans germline.
Journal Curr. Biol.
Abstract In sexually reproducing multicellular organisms, genetic information is propagated via the germline, the specialized tissue that generates haploid gametes. The C. elegans germline generates gametes in an assembly line-like process-mitotic divisions under the control of the stem cell niche produce nuclei that, upon leaving the niche, enter into meiosis and progress through meiotic prophase [1]. Here, we characterize the effects of perturbing cell division in the mitotic region of the C. elegans germline. We show that mitotic errors result in a spindle checkpoint-dependent cell-cycle delay, but defective nuclei are eventually formed and enter meiosis. These defective nuclei are eliminated by programmed cell death during meiotic prophase. The cell death-based removal of defective nuclei does not require the spindle checkpoint but instead depends on the DNA damage checkpoint. Removal of nuclei resulting from errors in mitosis also requires Spo11, the enzyme that creates double-strand breaks to initiate meiotic recombination. Consistent with this, double-strand breaks are increased in number and persist longer in germlines with mitotic defects. These findings reveal that the process of initiating meiotic recombination inherently selects against nuclei with abnormal chromosomal content generated by mitotic errors, thereby ensuring the genomic integrity of gametes.
Volume 23(23)
Pages 2400-6
Published 2013-12-2
DOI 10.1016/j.cub.2013.10.015
PII S0960-9822(13)01256-6
PMID 24239117
PMC PMC3885542
MeSH Animals Apoptosis / genetics Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Cell Nucleus / genetics DNA Breaks, Double-Stranded* DNA Repair / genetics* Endodeoxyribonucleases / genetics Germ Cells / cytology M Phase Cell Cycle Checkpoints Meiosis / genetics* Mitosis / genetics* RNA Interference RNA, Small Interfering Recombination, Genetic
IF 9.251
Times Cited 9
C.elegans tm1458