論文

国際誌
2020年10月

PCNA activates the MutLγ endonuclease to promote meiotic crossing over.

Nature
  • Dhananjaya S Kulkarni
  • ,
  • Shannon N Owens
  • ,
  • Masayoshi Honda
  • ,
  • Masaru Ito
  • ,
  • Ye Yang
  • ,
  • Mary W Corrigan
  • ,
  • Lan Chen
  • ,
  • Aric L Quan
  • ,
  • Neil Hunter

586
7830
開始ページ
623
終了ページ
627
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41586-020-2645-6

During meiosis, crossover recombination connects homologous chromosomes to direct their accurate segregation1. Defective crossing over causes infertility, miscarriage and congenital disease. Each pair of chromosomes attains at least one crossover via the formation and biased resolution of recombination intermediates known as double Holliday junctions2,3. A central principle of crossover resolution is that the two Holliday junctions are resolved in opposite planes by targeting nuclease incisions to specific DNA strands4. The endonuclease activity of the MutLγ complex has been implicated in the resolution of crossovers5-10, but the mechanisms that activate and direct strand-specific cleavage remain unknown. Here we show that the sliding clamp PCNA is important for crossover-biased resolution. In vitro assays with human enzymes show that PCNA and its loader RFC are sufficient to activate the MutLγ endonuclease. MutLγ is further stimulated by a co-dependent activity of the pro-crossover factors EXO1 and MutSγ, the latter of which binds Holliday junctions11. MutLγ also binds various branched DNAs, including Holliday junctions, but does not show canonical resolvase activity, implying that the endonuclease incises adjacent to junction branch points to achieve resolution. In vivo, RFC facilitates MutLγ-dependent crossing over in budding yeast. Furthermore, PCNA localizes to prospective crossover sites along synapsed chromosomes. These data highlight similarities between crossover resolution and the initiation steps of DNA mismatch repair12,13 and evoke a novel model for crossover-specific resolution of double Holliday junctions during meiosis.

リンク情報
DOI
https://doi.org/10.1038/s41586-020-2645-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32814343
ID情報
  • DOI : 10.1038/s41586-020-2645-6
  • PubMed ID : 32814343

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