title: 53BP1 contributes to a robust genomic stability in human fibroblasts.
abstract: Faithful repair of damaged DNA is a crucial process in maintaining cell viability and function. A multitude of factors and pathways guides this process and includes repair proteins and cell cycle checkpoint factors. Differences in the maintenance of genomic processes are one feature that may contribute to species-specific differences in lifespan. We predicted that 53BP1, a key transducer of the DNA damage response and cell cycle checkpoint control, is highly involved in maintaining genomic stability and may function differently in cells from different species. We demonstrate a difference in the levels and recruitment of 53BP1 in mouse and human cells following DNA damage. In addition, we show that unresolved DNA damage persists more in mouse cells than in human cells, as evidenced by increased numbers of micronuclei. The difference in micronuclei seems to be related to the levels of 53BP1 present in cells. Finally, we present evidence that unresolved DNA damage correlates with species lifespan. Taken together, these studies suggest a link between recruitment of 53BP1, resolution of DNA damage, and increased species lifespan.
authors.affiliation: Department of Pathology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Fink
authors.forename: Michaela
authors.initials: M
authors.lastname: Roell
authors.forename: Emanuela
authors.initials: E
authors.lastname: Caiazza
authors.forename: Chad
authors.initials: C
authors.lastname: Lerner
authors.forename: Thomas
authors.initials: T
authors.lastname: Stamato
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
authors.forename: Antonello
authors.initials: A
authors.lastname: Lorenzini
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072200:Ku Autoantigen; D008017:Life Expectancy; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen