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Agostinho, Ana, Meier, Bettina, Sonneville, Remi, Jagut, Marlène, Woglar, Alexander, Blow, Julian 
ORCID: https://orcid.org/0000-0002-9524-5849, Jantsch, Verena and Gartner, Anton
(2013)
Combinatorial regulation of meiotic holliday junction resolution in C. elegans by HIM-6 (BLM) helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 nucleases.
PLoS Genetics, 9 (7).
ISSN 1553-7390
Abstract
Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of "univalents" linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process.
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| Additional Information: | A correction is available for this article: There were errors in the Funding section. The correct funding information is as follows: This work was supported by grants from the Wellcome Trust Senior Research award (090944/Z/09/Z) to AG; the BBSRC studentship to AA; CRUK Grant C303/A7399 to JB; the Austrian FWF Grant P-23638-B12 and the Berta Karlik endowment from the University of Vienna. The Scottish University Life Sciences Alliance (SULSA) and the MRC grant MR/ K015869/1 supported the use of the OMX microscope, the Wellcome Trust grant 097045/B/11/Z provided infrastructure support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 2 Aug 2013: Agostinho A, Meier B, Sonneville R, Jagut M, Woglar A, et al. (2013) Correction: Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases. PLOS Genetics 9(8): 10.1371/annotation/d8c73205-151d-4e22-89c6-3aa574037d10. https://doi.org/10.1371/annotation/d8c73205-151d-4e22-89c6-3aa574037d10 View correction |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Jun 2024 10:31 |
| Last Modified: | 25 Sep 2024 17:51 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/95431 |
| DOI: | 10.1371/journal.pgen.1003591 |
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