Consequences For Genome Stability Research Articles

Epigenomics in stress tolerance of plants under the climate change.

Epigenomics in stress tolerance of plants under the climate change.

The SOS system: A complex and tightly regulated response to DNA damage.

Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli , this inducible system is termed the SOS response. The SOS global regulatory network consists of multiple factors promoting the integrity of DNA as well as error‐prone factors allowing for survival and continuous replication upon extensive DNA damage at the cost of elevated mutagenesis. Due to its mutagenic potential, the SOS response is subject to elaborate regulatory control involving not only transcriptional derepression, but also post‐translational activation, and inhibition. This review summarizes current knowledge about the molecular mechanism of the SOS response induction and progression and its consequences for genome stability. Environ. Mol. Mutagen. 60:368–384, 2019. © 2018 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Proteins Involved in DNA Double-Strand Breaks Repair Pathways Are Essential to Prevent the Development of Cancer

The single-stranded DNA binding (SSB) proteins play essential roles in the repair of many types of DNA damage, including double-stranded breaks (DSBs). Double-strand breaks (DSBs) are one of the severest types of DNA damage. The single-stranded binding protein is also important to maintain genome stability, since unrepaired DSBs easily induce cell death or chromosome aberrations. To maintain genome instability, cells have developed a cell-intrinsic network mechanism called DNA Damage Response (DDR) throughout most of the cell cycle. There are two main pathways of DSBs repair mechanisms, non-homologous end joining (NHEJ) and homology directed re¬pair (HR). In this perspective, we will describe how single-stranded DNA binding proteins functions during the DSB repair pathway and their consequences for genome stability and cancer.

DNA double-strand break repair pathway choice and cancer.

Since DNA double-strand breaks (DSBs) contribute to the genomic instability that drives cancer development, DSB repair pathways serve as important mechanisms for tumor suppression. Thus, genetic lesions, such as BRCA1 and BRCA2 mutations, that disrupt DSB repair are often associated with cancer susceptibility. In addition, recent evidence suggests that DSB "mis-repair", in which DSBs are resolved by an inappropriate repair pathway, can also promote genomic instability and presumably tumorigenesis. This notion has gained currency from recent cancer genome sequencing studies which have uncovered numerous chromosomal rearrangements harboring pathological DNA repair signatures. In this perspective, we discuss the factors that regulate DSB repair pathway choice and their consequences for genome stability and cancer.

Molecular Pathways: Transcription Factories and Chromosomal Translocations

The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer. The relationships between genome organization, transcription, and chromosomal translocation formation will have important implications in understanding the causes of therapy-related cancers.

Phase transitions and antichaos in generalized Kauffman networks

The critical properties of Kauffman networks with different input connectivities are studied. A general condition for stability is derived and used as a constraint (the antichaos constraint) in the calculation of the probability distribution of connections in a stable network. Some consequences for genome stability are outlined.

Phase transitions and antichaos in generalized Kauffman networks

The critical properties of Kauffman networks with different input connectivities are studied. A general condition for stability is derived and used as a constraint (the antichaos constraint) in the calculation of the probability distribution of connections in a stable network. Some consequences for genome stability are outlined.