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DNA Repair (Amst). 2017 Sep;57:66-75. doi: 10.1016/j.dnarep.2017.06.030. Epub 2017 Jul 3.

Differential effect of the overexpression of Rad2/XPG family endonucleases on genome integrity in yeast and human cells.

Author information

1
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER Universidad de Sevilla - CSIC - Universidad Pablo de Olavide Av. Américo Vespucio 24, 41092 Seville, Spain.
2
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER Universidad de Sevilla - CSIC - Universidad Pablo de Olavide Av. Américo Vespucio 24, 41092 Seville, Spain. Electronic address: aguilo@us.es.

Abstract

Eukaryotic cells possess several DNA endonucleases that are necessary to complete different steps in DNA metabolism. Rad2/XPG and Rad27/FEN1 belong to a group of evolutionary conserved proteins that constitute the Rad2 family. Given the important roles carried out by these nucleases in DNA repair and their capacity to create DNA breaks, we have investigated the effect that in vivo imbalance of these nucleases and others of the family have on genome integrity and cell proliferation. We show that overexpression of these nucleases causes genetic instability in both yeast and human cells. Interestingly, the type of recombination event and DNA damage induced suggest specific modes and timing of action of each nuclease that are beyond their known DNA repair function and are critical to preserve genome integrity. In addition to identifying new sources of genome instability, a hallmark of cancer cells, this study provides new genetic tools for studies of genome dynamics.

KEYWORDS:

Genetic instability; Homologous recombination; Rad2/XPG family; Rad27/FEN1

PMID:
28704715
DOI:
10.1016/j.dnarep.2017.06.030
[Indexed for MEDLINE]

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