Clarifying the mechanics of DNA strand exchange in meiotic recombination

Abstract

During meiosis, accurate separation of maternal and paternal chromosomes requires that they first be connected to one another through homologous recombination. Meiotic recombination has many intriguing but poorly understood features that distinguish it from recombination in mitotically dividing cells, and several of these features depend on the meiosis-specific DNA strand exchange protein Dmc1. Many questions about this protein have arisen since its discovery more than a decade ago, but recent genetic and biochemical breakthroughs promise to shed light on the unique behaviours and functions of this central player in the remarkable chromosome dynamics of meiosis.Sexual organisms must halve the chromosome number in gametes to maintain genome size with each generation. This goal is achieved through meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. The first meiotic division separates maternal and paternal copies of each chromosome, but in order for this segregation to occur properly, the chromosomes must first pair with their correct partner and then become physically connected so that they orient together on the meiotic spindle. Connection is established by the exchange of homologous chromosome arms (the point of crossover being called a "chiasma") plus cohesion between sister chromatids 1, 2 (Fig. 1). Exchange utilizes a specialized pathway of homologous recombination that repairs DNA double-strand breaks (DSBs) 3 -basically, the cell deliberately damages its own DNA and then uses the repair process to lock homologous chromosomes together. A central step in recombination involves proteins related to bacterial RecA, which catalyze the pairing and exchange of DNA strands between single-stranded DNA (ssDNA) formed at the break and intact, homologous double-stranded DNA (dsDNA) 4 . Most eukaryotes have two RecA homologues, the ubiquitous Rad51 and its meiosis-specific counterpart Dmc1 (ref. 5).Meiotic recombination is subject to many layers of control that dictate, for example, the choice of DNA substrate for DSB repair, the distribution and timing of recombination events, and the integration of recombination with higher order chromosome structures 2,6 . Executing these controls requires meiosis-specific factors (such as Dmc1) in addition to Reprints and permissions information is available at npg.nature.com/reprintsandpermissions.

BRCA2: a universal recombinase regulator

“…Meiosis is a key event in the life cycle of all sexually reproducing organisms. It promotes the transition from diploid to haploid phase, and during this process it is essential that the maternal and paternal chromosomes recombine before the production of progeny (Neale and Keeney, 2006). The basic mechanism of recombination during meiosis is remarkably similar to that which can occur in somatic cells, but a few key features mark important differences (Figure 2).…”

Meiotic double strand breaks repair in sexually reproducing eukaryotes: We are not all equal

“…Strand invasion of homologous chromosome by the 3′ single strand is mediated by members of the RecA family: namely RAD51 and the meiotic-specific DMC1. Removal of Spo11 from meiotic DSB ends involves in yeast the Sae2 and Mre11-Rad50-Xrs2-dependent endonucleolytic step that releases Spo11 bound to a short nucleotide sequence [12,13].…”

Recent advance in our understanding of the molecular nature of chromosomal abnormalities

“…60,61 There is an emerging consensus that the events that occur during prophase in meiosis I are essential for the proper segregation of homologous chromosomes. 62 Homologous chromosomes that behave independently during mitotic division have to segregate into two different daughter cells in meiosis I. To accomplish this process, homologous chromosomes interact with each other utilizing a specialized HR pathway (Figure 4a).…”