Double-stranded DNA breaks and gene functions in recombination and meiosis

Abstract

Gene functions in recombination and meiosis 402 npg REVIEW Meiotic prophase I is a long and complex phase. Homologous recombination is an important process that occurs between homologous chromosomes during meiotic prophase I. Formation of chiasmata, which hold homologous chromosomes together until the metaphase I to anaphase I transition, is critical for proper chromosome segregation. Recent studies have suggested that the SPO11 proteins have conserved functions in a number of organisms in generating sites of double-stranded DNA breaks (DSBs) that are thought to be the starting points of homologous recombination. Processing of these sites of DSBs requires the function of RecA homologs, such as RAD51, DMC1, and others, as suggested by mutant studies; thus the failure to repair these meiotic DSBs results in abnormal chromosomal alternations, leading to disrupted meiosis. Recent discoveries on the functions of these RecA homologs have improved the understanding of the mechanisms underlying meiotic homologous recombination.Cell Research (2006) Meiosis is a highly coordinated cell division, which generates four haploid reproductive cells required for sexual reproduction. Meiosis involves one round of DNA replication and two nuclear divisions, meiosis I and meiosis II. The first nuclear division leads to the segregation of homologous chromosomes (homologs), and is unique to meiosis. During the second division, sister chromatids are separated, resulting in the formation of four haploid nuclei and followed by the meiotic cytokinesis that forms four haploid cells. Similar to mitosis, both meiosis I and meiosis II can be divided into four stages: prophase, metaphase, anaphase, and telophase.However, meiosis I differs from meiosis II as meiosis I involves homology search, pairing, interhomolog recombination, and synapsis of homologs, processes that are required for correct association and segregation of homologs. The prophase stage of meiosis I, or prophase I, has been the target of interest because of the occurrence of these major processes of chromosome interactions. During early prophase I, arms of sister chromosomes are closely associated by protein complexes called cohesins, which are removed during the metaphase I/anaphase I transition. However, the centromere regions remained associated until the segregation of sister chromatids during meiosis II. Homologous pairing is the result of interaction between homologous chromosomes relying on the homology of DNA sequences [1,2], and is considered to be a transient and non-stable association between homologous chromosomes. Pairing between homologous chromosomes facilitates the process of recombination. The recombination process confers the interexchange of genetic information between non-sister chromatids, and generates chiasmata, which ensure proper association between homologous chromosomes prior to chromosome segregation at anaphase I. Synapsis, however, is a stable association by forming synaptonemal complexes between chromosomes. Synaptonemal complexes are threeparti...

Origins and evolution of the recA / RAD51 gene family: Evidence for ancient gene duplication and endosymbiotic gene transfer

“…Gene duplication allows one copy to maintain the existing function and the other to gain a new function. Specifically, the genes in the RAD␣ subfamily are important for homologous recombination and DNA repair, which are similar to the eubacterial recA functions (12,13,17,28,29), suggesting that these genes have maintained the original function.…”

“…For example, disruption of the mouse RAD51 gene can lead to cell death and embryo inviability (17). The DMC1 gene is specifically required for meiotic recombination in yeast, plants, and animals (12). Similarly, the RAD51, RAD51C, and XRCC3 homologs in Arabidopsis are also essential for meiosis (12,13).…”

“…Eukaryotic RAD51-like genes play important roles in homologous recombination, maintaining chromosomal integrity in both the mitotic and meiotic cell cycles (12,16). For example, disruption of the mouse RAD51 gene can lead to cell death and embryo inviability (17).…”

“…The DMC1 gene is specifically required for meiotic recombination in yeast, plants, and animals (12). Similarly, the RAD51, RAD51C, and XRCC3 homologs in Arabidopsis are also essential for meiosis (12,13). Although all RAD51-like genes promote homologous recombination, they may have distinct functions (18).…”

“…Among eukaryotes, the budding yeast and the fission yeast Schizosaccharomyces pombe contain four RAD51-like genes (RAD51, DMC1, RAD55͞rhp55, and RAD57͞rhp57) (5,6,10,11). In vertebrate animals and plants, there are usually seven different RAD51-like genes: RAD51, RAD51B, RAD51C, RAD51D, DMC1, XRCC2, and XRCC3 (Table 1) (12,13). In addition, the flowering plants Arabidopsis thaliana and rice (Oryza sativa) each possess four conserved recA-like genes (refs.…”