The budding yeast Saccharomyces cerevisiae has been the principal organism used in experiments to examine genetic recombination in eukaryotes. Studies over the past decade have shown that meiotic recombination and probably most mitotic recombination arise from the repair of double-strand breaks (DSBs). There are multiple pathways by which such DSBs can be repaired, including several homologous recombination pathways and still other nonhomologous mechanisms. Our understanding has also been greatly enriched by the characterization of many proteins involved in recombination and by insights that link aspects of DNA repair to chromosome replication. New molecular models of DSB-induced gene conversion are presented. This review encompasses these different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.

/pdf/multiple-pathways-of-recombination-induced-by-double-strand-1c7668ukfa.pdf

Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae

https://mcb.berkeley.edu/courses/mcb230/WEB/PAPERS/jenuwein%20cell%20suv39%20genome%20stability%20copy.pdf

Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.

Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.

Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.

Homologous recombination (HR) serves to eliminate deleterious lesions, such as double-stranded breaks and interstrand crosslinks, from chromosomes. HR is also critical for the preservation of repli- cation forks, for telomere maintenance, and chromosome segrega- tion in meiosis I. As such, HR is indispensable for the maintenance of genome integrity and the avoidance of cancers in humans. The HR reaction is mediated by a conserved class of enzymes termed recombinases. Two recombinases, Rad51 and Dmc1, catalyze the pairing and shuffling of homologous DNA sequences in eukaryotic cells via a filamentous intermediate on ssDNA called the presynaptic filament. The assembly of the presynaptic filament is a rate-limiting process that is enhanced by recombination mediators, such as the breast tumor suppressor BRCA2. HR accessory factors that facil- itate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified. Recent progress on elucidating the mechanisms of action of Rad51 and Dmc1 and their cohorts of ancillary factors is reviewed here.

https://www.med.nyu.edu/klein/PDFs/annurev.biochem.77.061306.125255.pdf

Mechanism of eukaryotic homologous recombination.

Cancer/testis (CT) antigens, of which more than 40 have now been identified, are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumour types, including melanoma, and carcinomas of the bladder, lung and liver These immunogenic proteins are being vigorously pursued as targets for therapeutic cancer vaccines CT antigens are also being evaluated for their role in oncogenesis — recapitulation of portions of the germline gene-expression programme might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, hypomethylation and metastatic capacity

Cancer/testis antigens, gametogenesis and cancer.

Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.

Meiosis is an essential stage in gamete formation in all sexually reproducing organisms. Studies of mutations in model organisms and of human haplotype patterns are leading to a clearer understanding of how meiosis has adapted from yeast to humans, the genes that control the dynamics of chromosomes during meiosis, and how meiosis is tied to gametic success. Genetic disruptions and meiotic errors have important roles in infertility and the aetiology of developmental defects, especially aneuploidy. An understanding of the regulation of meiosis, coupled with advances in genomics, may ultimately allow us to diagnose the causes of meiosis-based infertilities, more wisely apply assisted reproductive technologies, and derive functional germ cells.

Genetics of mammalian meiosis: regulation, dynamics and impact on fertility

We review what is known about the transcriptional inactivation and condensation of heteromorphic sex chromosomes in contrast to the activation of homomorphic sex chromosomes during meiotic prephase in animals. We relate these cytological and transcriptional features to the recombination status of the sex chromosomes. We propose that sex chromosome condensation is a meiotic adaptation to prevent the initiation of potentially damaging recombination events in nonhomologous regions of the X and Y chromosome.

Sex chromosomes, recombination, and chromatin conformation

The XY body: a specialized meiotic chromatin domain

https://www.repository.cam.ac.uk/bitstream/1810/291664/1/Ultra-High%20Resolution%203D%20Imaging%20of%20Whole%20Cells.pdf

Mary Ann Handel

Papers

Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.

Genetics of mammalian meiosis: regulation, dynamics and impact on fertility

Sex chromosomes, recombination, and chromatin conformation

The XY body: a specialized meiotic chromatin domain

Ultra-High Resolution 3D Imaging of Whole Cells