RRC ID 45917
著者 Agostinho A, Meier B, Sonneville R, Jagut M, Woglar A, Blow J, Jantsch V, Gartner A.
タイトル 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.
ジャーナル PLoS Genet
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.
巻・号 9(7)
ページ e1003591
公開日 2013-1-1
DOI 10.1371/journal.pgen.1003591
PII PGENETICS-D-12-02828
PMID 23901331
PMC PMC3715425
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Chromatin / genetics Chromosome Segregation / genetics Crossing Over, Genetic DNA Breaks, Double-Stranded DNA Helicases / genetics* DNA, Cruciform / genetics* DNA-Binding Proteins / genetics* Deoxyribonucleases / genetics* Endonucleases / genetics* Humans Meiosis / genetics* Meiotic Prophase I / genetics Mice Mutation Recombination, Genetic
IF 5.175
引用数 52
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm2644 tm1981 tm1937 tm2842