Chromatin structure contribution to the synaptonemal complex formation

Meiosis is a key cellular and molecular process for sexual reproduction contributing to the genetic variability of organisms. This process takes place after DNA replication and consists in a double cellular division, giving rise to four haploid daughter cells or gametes. Meiotic recombination between homologous chromosomes, in the meiotic prophase I, is mediated by a tripartite structure named Synaptonemal Complex (SC). The SC is a peptidic scaffold in which the chromatin of homologous chromosomes is organized during the pachytene stage, holding chromosomes together until the meiotic recombination and genetic exchange have taken place. The role of chromatin structure in formation of the SC and the meiotic recombination at meiotic prophase I remain largely unknown. In this review we address the epigenome contribution to the SC formation at meiotic prophase I, with particular attention on the chromatin structure modifications occurring during the sub-stages of meiotic prophase I. Received 18 September 2008; received after revision 10 October 2008; accepted 24 October 2008     

RecQ helicases and topoisomerases: components of a conserved complex for the regulation of genetic recombination

Maintenance of genomic stability relies on the efficient and accurate execution of DNA repair pathways, and is essential for cell viability and the prevention of cancer. Mutation of genes encoding RecQ helicases or topoisomerases gives rise to genomic instability through excessive recombination. Here, we review the recent biochemical and genetic evidence to indicate that these two classes of protein act in concert in a conserved pathway to maintain genomic stability by preventing inappropriate recombination.     

The BLM dissolvasome in DNA replication and repair

RecQ DNA helicases are critical for proper maintenance of genomic stability, and mutations in multiple human RecQ genes are linked with genetic disorders characterized by a predisposition to cancer. RecQ proteins are conserved from prokaryotes to humans and in all cases form higher-order complexes with other proteins to efficiently execute their cellular functions. The focus of this review is a conserved complex that is formed between RecQ helicases and type-I topoisomerases. In humans, this complex is referred to as the BLM dissolvasome or BTR complex, and is comprised of the RecQ helicase BLM, topoisomerase IIIα, and the RMI proteins. The BLM dissolvasome functions to resolve linked DNA intermediates without exchange of genetic material, which is critical in somatic cells. We will review the history of this complex and highlight its roles in DNA replication, recombination, and repair. Additionally, we will review recently established interactions between BLM dissolvasome and a second set of genome maintenance factors (the Fanconi anemia proteins) that appear to allow coordinated genome maintenance efforts between the two systems.