Meiotic and Mitotic Recombination in Meiosis

Abstract

Meiotic crossovers facilitate the segregation of homologous chromosomes and increase genetic diversity. The formation of meiotic crossovers was previously posited to occur via two pathways, with the relative use of each pathway varying between organisms; however, this paradigm could not explain all crossovers, and many of the key proteins involved were unidentified. Recent studies that identify some of these proteins reinforce and expand the model of two meiotic crossover pathways. The results provide novel insights into the evolutionary origins of the pathways, suggesting that one is similar to a mitotic DNA repair pathway and the other evolved to incorporate special features unique to meiosis. MEIOSIS is essential to maintaining the proper complement of chromosomes in sexually reproducing organisms. By following one round of DNA replication with two rounds of cellular division, meiosis effectively halves the chromosome content of participating cells. Prior to the first meiotic division, homologous chromosomes pair and, in many organisms, undergo recombination. Both crossovers, characterized by the reciprocal exchange of flanking markers, and noncrossovers, in which flanking DNA remains unchanged, result from these recombination events. Crossovers can also occur in mitotically proliferating cells during repair of certain types of DNA damage, especially double-strand breaks. Meiotic crossovers likewise are initiated from double-strand breaks, and many of the proteins used in mitotic repair are also used in meiotic recombination. This has led to the suggestion that meiotic recombination evolved from mitotic recombination (Marcon and Moens 2005). However, several modifications were necessary to give rise to meiotic recombination in its current form (reviewed in Villeneuve and Hillers 2001). First, a mechanism of generating programmed double-strand breaks to initiate recombination was needed. This was achieved through the use of Spo11, a conserved protein that generates regulated meiotic double-strand breaks (Keeney et al. 1997). Second, whereas crossovers are avoided in mitotic cells to prevent loss of heterozygosity and chromosome rearrangement, crossover formation is emphasized in meiotic recombination to facilitate the segregation of homologous chromosomes and to increase genetic diversity. Third, the preferred repair template was changed from the sister chromatid in mitotic cells to the homologous chromosome in meiotic cells, since only crossovers between homologs give the aforementioned benefits. Finally, exquisite crossover control mechanisms arose to regulate the number and distribution of crossovers across the genome and relative to one another. In particular, every chromosome pair receives at least one crossover, sometimes called an obligate crossover (Jones 1984). Also, if additional crossovers occur, they tend not to be near one another, a phenomenon called crossover interference (reviewed in Berchowitz and Copenhaver 2010).A complication obscuring the relationship between the mitotic and meiot...

DNA Helicase HIM-6/BLM Both Promotes MutSγ-Dependent Crossovers and Antagonizes MutSγ-Independent Interhomolog Associations During Caenorhabditis elegans Meiosis

“…While it has been suggested that MutSg promotes COs primarily by antagonizing the functions of helicases that would dismantle CO intermediates (Kohl and Sekelsky 2013), we have found that in the context of C. elegans meiosis, the requirements for MutSg and its partner COSA-1 in chiasma formation are not bypassed by eliminating either HIM-6/BLM (this work) or RTEL-1 (Yokoo et al 2012). We suggest that instead of (or in addition to) antagonizing anti-CO helicases, MutSg and other pro-CO factors may be needed to antagonize inappropriate resolvase activities, to recruit appropriate resolvases, to recruit HIM-6/BLM, and/or to preserve the structure of the intermediates in a form that confers biased resolution.…”

“…Recent evidence suggests that checkpoint-like feedback mechanisms operate to ensure both that DSB formation continues until each homolog pair has at least one CO-eligible recombination intermediate and that DSB formation will shut down once this condition is met Stamper et al 2013). Following DSB formation, a subset of the initial recombination intermediates is selected to become COs, recruiting a cohort of CO-promoting (pro-CO) proteins that function to stabilize and protect these COdesignated intermediates (Baudat and De Massy 2007;Kohl and Sekelsky 2013;Lynn et al 2007). A widely conserved solution for protecting potential CO intermediates involves the MutSg complex, comprising MSH4 and MSH5, meiosisspecific members of the MutS protein family that can form a sliding clamp on DNA in response to recognition of branched DNA structures (Baudat and De Massy 2007;Lynn et al 2007;Snowden et al 2004).…”

Coding and noncoding variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B affect recombination rate in cattle

“…The present model postulates two mitoticlike pathways (leading, respectively, to noncrossovers and crossovers [COs] that are not subject to chromosome interference), and one meiosis-specific pathway (leading to COs that are subject to chromosome interference) (e.g., Kohl and Sekelsky 2013). Many genes have been identified that, upon mutation, affect meiotic recombination.…”

Sources and Structures of Mitotic Crossovers That Arise When BLM Helicase Is Absent inDrosophila

“…Since that time, a great deal has been learned about the functions, molecular mechanisms, and regulation of meiotic recombination. This process is initiated through the introduction of programmed DNA doublestrand breaks (DSBs), which are then repaired through highly regulated homologous recombination (HR) pathways such that a substantial fraction of repair events produce reciprocal crossovers (reviewed in Kohl and Sekelsky 2013). The chiasmata that form at sites of crossovers help to ensure accurate segregation of homologous chromosomes.…”