Maria Lab Report

Introduction

Sexual reproduction in animals requires the generation of haploid gametes from diploid germ cells by the specialized cell division cycle of meiosis. The ploidy is halved because one round of pre-meiotic DNA replication is followed by two rounds of chromosome segregation during meiosis. Homologous chromosomes and sister chromatids segregate during the first and second rounds of meiotic nuclear divisions, respectively. Orderly segregation of homologous chromosomes requires that homologous chromosomes become physically linked through inter-homologue crossovers during the first meiotic prophase. Crossovers are formed by a modified homologous recombination pathway specific to meiosis. This entails the active generation of DNA double

This alignment of chromosome axes leads to the formation of a meiosis-specific chromatin structure, the synaptonemal complex, which assembles along each pair of homologous chromosomes as cells progress to the pachytene stage of prophase. Efficient crossover formation depends on synaptonemal complex formation during meiosis. Thus, each pair of homologous chromosomes must engage into synapsis to ensure correct chromosome segregation during the first meiotic division and to prevent generation of gametes with incorrect chromosome sets. Accordingly, asynapsis is monitored during meiosis, and persistent asynapsis seems to trigger elimination of meiocytes in mammals. Survaillance mechanisms that eliminate asynaptic meiocytes involve the recruitment of ATR activity specifically to unsynapsed chromosome regions. ATR activity leads to the accumulation of a phosphorylated form of histone H2AX, called γH2AX, and to meiotic silencing of unsynapsed chromatin (MSUC). It is thought that persistent asynapsis triggers oocyte elimination either due to direct activation of apoptotic signaling cascades by persistent ATR activity, or due to inappropriate silencing of essential genes on

The sex chromosomes are largely non-homologous, hence they synapse only in their short homologous PAR regions during the pachytene stage of prophase where autosomal chromosomes are fully synapsed. As a consequence, the unsynapsed regions of sex chromosomes are silenced, and are incorporated into a distinct γH2AX-rich chromatin domain, called the sex body. Crucially, the silencing of sex chromosomes is essential for progression of spermatocytes beyond mid-pachytene because there are genes on sex chromosomes whose expression is incompatible with spermatocyte survival at this stage. It is believed that the requirement for sex chromosome silencing provides an effective mechanism for the elimination of asynaptic spermatocytes. Abnormal autosomal asynapsis titrates ATR activity away from sex chromosomes resulting in imperfect silencing of sex chromosomes and the expression of genes that are toxic to spermatocytes in mid-pachytene. Thus, MSUC and sex body formation are important components of the surveillance mechanisms that safeguard the quality of gametogenesis in mammals. Interestingly, the sex body is accompanied by an enigmatic nuclear structure that was termed the dense body due to its high electron-density in