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Research Paper|Volume 3, Issue 9|pp 836—845

53BP1 contributes to a robust genomic stability in human fibroblasts

Lauren S. Fink1,4, Michaela Roell2, Emanuela Caiazza2, Chad Lerner1, Thomas Stamato3, Silvana Hrelia2, Antonello Lorenzini2, Christian Sell1
  • 1Department of Pathology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
  • 2Department of Biochemistry, “G. Moruzzi” University of Bologna, Bologna, Italy
  • 3Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA
  • 4Department of Cancer Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Received: August 17, 2011Accepted: September 12, 2011Published: September 8, 2011

Copyright: © 2011 Fink et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.