Studies of Aurora and Polo Kinases During Cell Division in C. elegans

Accurate chromosome segregation during cell division requires the precisely regulated release of chromosome cohesion. In mitosis, sister chromatids are linked by chromosome cohesion until the proteolysis of the cohesion Scc1 by separase triggers the separation of sister chromatids at anaphase. Chromosome dynamics during meiosis are more complex, as homologous chromosomes separate in anaphase I, whereas sister chromatids remain attached until anaphase II. In meiosis, separase must cleave the cohesin REC-8 in a stepwise manner to separate homologs in meiosis I and then sister chromatids in meiosis II. However, the mechanisms regulating the selective and sequential release of meiotic chromosome cohesion are unclear. Using C. elegans, we investigated the roles of Aurora and Polo kinases during the release of meiotic chromosome cohesion. We found that the Aurora B kinase AIR-2 is localized to sub-chromosomal regions representing the last points of contact between homologous chromosomes in meiosis I and between sister chromatids in meiosis II. Depletion of AIR-2 by RNA interference (RNAi) prevented both chromosome separation and REC-8 removal during meiosis. We showed AIR-2 phosphorylated REC-8 at a major amino acid in vitro (T625). The depletion of two phosphatases, GSP-1 and GSP-2, altered the localization pattern of AIR-2, such that AIR-2 is detected throughout the chromosome. Concurrently, there was a chromosome-wide reduction in REC-8 and sister chromatids precociously separated at anaphase I. We propose that AIR-2 promotes the selective release of meiotic chromosome cohesion via the phosphorylation of REC-8 at specific chromosomal locations and that GSP-1/2 antagonize AIR-2 activity. We also described that the Polo-like kinase PLK-1 is required for the release of meiotic chromosome cohesion during meiosis II. Depletion of PLK-1 by RNAi did not block the separation of homologous chromosomes, but the resulting dyads fail to separate during meiosis II. Furthermore, in plk-1(RNAi) embryos, REC-8 was not removed from these dyads. PLK-1 was capable of phosphorylating REC-8 in vitro. The gsp-1/2(RNAi) phenotype of precocious loss of REC-8 at anaphase I was suppressed by the simultaneous inhibition of PLK-1. We propose PLK-1 regulates the second phase of meiotic chromosome cohesion release. In summary, we propose that both Aurora B and Polo kinases phosphorylate REC-8 in order to regulate the selective and sequential release of chromosome cohesion during meiosis in C. elegans.

Author dc:creator

• Rogers, Eric Jason

Contributors dc:contributor

• Lin, Rueyling

• Cell Division
• Aurora Kinase
• Caenorhabditis elegans

Language dc:language

en

Identifier

60572816

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/657