Figure 3

Proposed connection between HJ resolution defect and abnormalities in Rad51c mutant oocytes at metaphase II. During meiosis, HJs are established between homologous chromosomes by the pachytene stage of prophase I using the homologous recombination machinery. At metaphase I, bivalents are pulled in opposite directions by microtubules attached to kinetochores of sister chromatids that are oriented toward the same pole. While centromeric cohesion is protected by Shugoshin to ensure that sister chromatids stay together during the reductional division, cohesion is released along the chromosome arms. During anaphase I, homologous chromosomes segregate to separate cells. In the absence of chiasmata, homologous chromosomes do not align properly at the metaphase plate, and this activates a spindle checkpoint resulting in metaphase I arrest. In Rad51c-deficient oocytes, meiosis progresses normally until anaphase I. However, due to accumulation of recombination intermediates, such as double Holliday junctions (dHJs), which hold the homologous chromosomes together, there is an increase in tension at the centromere due to the persistence of unresolved dHJs. The increased tension is thought to disrupt the sister chromatid cohesion at the centromere, resulting in the PSSC phenotype and fragmented chromosomes. Homologous chromosomes are shown in red and green; REC8 is shown in yellow; shugoshin is orange; and centromeres are shown in purple. (Reproduced from The Journal of Cell Biology, 2007, 176:581–592, Copyright 2007 The Rockefeller University Press.)