Behavior of dicentric chromosomes in budding yeast

• Published in: PLoS genetics Vol. 17; no. 3; p. e1009442
• Main Authors: Cook, Diana, Long, Sarah, Stanton, John, Cusick, Patrick, Lawrimore, Colleen, Yeh, Elaine, Grant, Sarah, Bloom, Kerry
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.03.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Biology and Life Sciences; Brewer's yeast; Cell cycle; Cell viability; Centromeres; Chromosome 4; Chromosome IV; Chromosomes; Cytology; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Genetic aspects; Genomes; Glucose; LIF1 protein; Non-homologous end joining; Observations; Plasmids; Proteins; Rad52 protein; Research and Analysis Methods; Ribosomal DNA; Yeast; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009442

DNA double-strand breaks arise in vivo when a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two centromeres attached to opposite spindle pole bodies. Repair of the DSBs generates phenotypic diversity due to the range of monocentric derivative chromosomes that arise. To explore whether DSBs may be differentially repaired as a function of their spatial position in the chromosome, we have examined the structure of monocentric derivative chromosomes from cells containing a suite of dicentric chromosomes in which the distance between the two centromeres ranges from 6.5 kb to 57.7 kb. Two major classes of repair products, homology-based (homologous recombination (HR) and single-strand annealing (SSA)) and end-joining (non-homologous (NHEJ) and micro-homology mediated (MMEJ)) were identified. The distribution of repair products varies as a function of distance between the two centromeres. Genetic dependencies on double strand break repair (Rad52), DNA ligase (Lif1), and S phase checkpoint (Mrc1) are indicative of distinct repair pathway choices for DNA breaks in the pericentromeric chromatin versus the arms.