Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes

Abstract

Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms must devise strategies to couple sister chromatids so that they stay together during the first meiotic division (when homologous chromosomes separate) and then segregate away from one another during the second division. Here we review recent findings that shed light on how Caenorhabditis elegans, an organism with holocentric chromosomes, deals with these challenges of meiosis by differentiating distinct chromosomal subdomains and remodeling chromosome structure during prophase. Furthermore, we discuss how features of chromosome organization established during prophase affect later chromosome behavior during the meiotic divisions. Finally, we illustrate how analysis of holocentric meiosis can inform our thinking about mechanisms that operate on monocentric chromosomes.During sexual reproduction, diploid chromosome number must be reduced in half to generate haploid gametes. This reduction in chromosome number is accomplished during meiosis, a specialized cell division program in which a single round of DNA replication is followed by two rounds of chromosome segregation. During prophase of meiosis I, homologous chromosomes pair, align, and undergo crossover recombination between their DNA molecules. These crossovers collaborate with sister chromatid cohesion (SCC) to create temporary physical links, called chiasmata, that connect homologs and allow them to orient and then segregate toward opposite poles of the meiosis I spindle, thereby achieving reduction in ploidy. The reductional meiosis I division is followed by an equational meiosis II division, akin to mitosis, in which sister chromatids are segregated to opposite spindle poles.Chromosome segregation during meiosis presents two special challenges for the cell division machinery: (1) SCC must be released in two steps. This is necessary to allow release of chiasmata and reductional segregation in meiosis I, while retaining a local region of sister cohesion necessary to align chromosomes and to maintain sister connections until anaphase of meiosis II. (2) Sister chromatids must be temporarily ''co-oriented'' during meiosis I, so that they move together to the same spindle pole. Sister chromatids must then switch their behavior, becoming ''bioriented'' on the meiosis II spindle so that they can move apart toward opposite spindle poles.In organisms with monocentric chromosomes, the single localized centromere serves as the focal point for mechanisms that serve to co-orient sister chromatids at meiosis I and for mechanisms that promote local protection of cohesion to allow two-step release of SCC (Sakuno and Watanabe 2009). In contrast, organisms with holocentric chromosomes, which do not have a localized centromere, cannot rely on a single predefined site to regulate sister chromatid co-orientation and the two-step loss of cohesion during meiosis.Although monocentric chromosome organization is more...

Manipulation of Karyotype inCaenorhabditis elegansReveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis

“…Cohesin complexes play multiple roles during the meiotic program, promoting pairing, synapsis, and recombination between homologs during meiotic prophase and mediating regulated segregation during the meiotic divisions (Pasierbek et al 2001;Chan et al 2003;Severson et al 2009;Schvarzstein et al 2010). During wild-type meiosis, sister chromatid cohesion is released in two steps, enabling reductional segregation of homologs at meiosis I, followed by equational segregation of sister chromatids at meiosis II.…”

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

“…We localized a boundary between a low-rate chromosomal center and a high-rate chromosomal arm to an interval of just a few kilobases. In C. elegans, a single off-center crossover plays a critical role in specifying chromatid cohesion and orientation during prophase (Schvarzstein et al 2010), and the crossover rate domain structure may be a signature of underlying structural features that quantitatively exclude crossovers from the chromosome centers. The discrete boundary we have identified holds promise for identifying these structural features.…”

“…The preference for chromosome arms may relate to the mechanical requirements for meiotic chromosome segregation in a species lacking discrete centromeres. An off-center crossover defines an acting "short arm" and "long arm" of each bivalent, and different proteins localize to each of these arms to facilitate appropriate regulation of sister-chromatid cohesion (reviewed by Schvarzstein et al 2010). Because the short and long arm are defined randomly in each meiosis, their designation depends on chomosome-wide communication of the crossover location and a clear distinction between short and long.…”

Different roles for Aurora B in condensin targeting during mitosis and meiosis

“…On the holocentric chromosomes of worms, the lack of a localized centromere necessitates coordination of meiotic events in a different manner (reviewed by Schvarzstein et al, 2010). During worm meiosis, the site of the crossover, and not a localized region of centromeric CENP-A-containing chromatin, ultimately determines the plane of chromosome orientation and the site of cohesion release (Monen et al, 2005;Nabeshima et al, 2005).…”