A decade of understanding spatio-temporal regulation of DNA repair by the nuclear architecture.
The nucleus is a hub for gene expression and is a highly organized entity. The nucleoplasm is heterogeneous, owing to the preferential localization of specific metabolic factors, which lead to the definition of nuclear compartments or bodies. The genome is organized into chromosome territories, as well as heterochromatin and euchromatin domains. Recent observations have indicated that nuclear organization is important for maintaining genomic stability. For example, nuclear organization has been implicated in stabilizing damaged DNA, repair-pathway choice, and in preventing chromosomal rearrangements. Over the past decade, several studies have revealed that dynamic changes in the nuclear architecture are important during double-strand break repair. Stemming from work in yeast, relocation of a damaged site prior to repair appears to be at least partially conserved in multicellular eukaryotes. In this review, we will discuss genome and nucleoplasm architecture, particularly the importance of the nuclear periphery in genome stability. We will also discuss how the site of relocation regulates repair-pathway choice.
Southern Alberta Cancer Research Institute, Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine; University of Calgary; 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada.|Southern Alberta Cancer Research Institute, Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine; University of Calgary; 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada.
Hicham
H
Saad
Southern Alberta Cancer Research Institute, Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine; University of Calgary; 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada.|Southern Alberta Cancer Research Institute, Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine; University of Calgary; 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada.
Jennifer A
JA
Cobb
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans
D002843:Chromatin
DNA damage; chromatin; chromatine; corps nucléaires; dommage à l’ADN; nuclear bodies; nuclear periphery; périphérie nucléaire