2019 Fiscal Year Annual Research Report
Mechanisms that promote the correct completion of meiosis by breaking symmetry of chromosomes
| Project/Area Number |
18H02373
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
Carlton Peter 京都大学, 生命科学研究科, 准教授 (20571813)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | 減数分裂 / 線虫 / 染色体ダイナミクス |
|---|
| Outline of Annual Research Achievements |
1. We determined the partitioning of phosphorylated SYP-1 protein is a faster and earlier mode of the partitioning of bulk SYP-1 to the "short arm" of chromosomes. We determined this by HA-tagging a non-phosphorylatable version of SYP-1, and showed that it became enriched on the short arm before bulk SYP-1, indicating that the short arm becomes enriched for both phosphorylated and non-phosphorylated SYP-1; further, in spo-11 mutants lacking programmed double-strand breaks, migration of bulk SYP-1 to rare chromosomes with DNA damage is preceded by migration of phosphorylated SYP-1. We conclude phosphorylation of SYP-1 enhances its dynamic partitioning.
2. Our preliminary work has determined that the feedback loop specifying phosphorylation of SYP-1 on the short arm likely involves the regulatory phosphatase CDC-25.4 in C. elegans. Depletion of this phosphatase by RNAi leads to lack of partitioning in a subset of chromosomes.
3. We showed that phosphomutations of HIM-3 lead to failure of partitioning of SYP-1 and HTP-1. This strongly suggests cross-talk between lateral element HORMA-domain proteins and central element proteins of the SC is important for correct partitioning and therefore for correct segregation.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We have accumulated enough data in the first two years to form the major part of two manuscripts that we intend to submit by the end of the current fiscal year; of these two, we expect to have one accepted by the end of the current fiscal year. Further, the experiments carried out during this project have already laid the groundwork for future work in this area, as we discover more about the feedback loops that connect crossovers to synaptonemal complex phosphorylation.
|
| Strategy for Future Research Activity |
We will proceed as outlined in our proposal, and work on both SYP-1 and HIM-3 asymmetric phosphorylation. We will determine the kinase(s) that phosphorylate(s) HIM-3 and understand the role it plays in chromosome dynamics. We will elucidate the mechanism through which phosphorylation of SYP-1 and HIM-3 are restricted to the short arm, while HTP-1 and LAB-1 is restricted to the long arm, thereby establishing the domains of early and late cohesin loss, respectively.
|
