Removal of reactive oxygen species-induced 3'-blocked ends by XPF-ERCC1.
XPF-ERCC1 is a structure-specific endonuclease that is essential for nucleotide excision repair and DNA interstrand cross-link repair in mammalian cells. The yeast counterpart of XPF-ERCC1, Rad1-Rad10, plays multiple roles in DNA repair. Rad1-Rad10 is implicated to be involved in the repair of oxidative DNA damage. To explore the role(s) of XPF-ERCC1 in the repair of DNA damage induced by reactive oxygen species (ROS), cellular sensitivity of the XPF-deficient Chinese hamster ovary cell line UV41 to ROS was investigated. The XPF-deficient UV41 showed sensitivity to hydrogen peroxide, bleomycin, and paraquat. Furthermore, XPF-ERCC1 showed an ability to remove 3'-blocked ends such as 3'-phosphoglycolate from the 3'-end of DNA in vitro. These data suggest that XPF-ERCC1 plays a role in the repair of ROS-induced DNA damage by trimming 3'-blocked ends. The accumulation of various types of DNA damage, including ROS-induced DNA damage due to defects in multiple XPF-ERCC1-mediated DNA repair pathways, could contribute to the accelerated aging phenotypes observed in an XPF-ERCC1-deficient patient.
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Laura A
LA
Fisher
Laura
L
Samson
Tadayoshi
T
Bessho
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects / Q000494:pharmacology; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000172:deficiency / Q000235:genetics*; D017353:Gene Deletion; D006016:Glycolates / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000494:pharmacology; D010084:Oxidation-Reduction; D010269:Paraquat / Q000009:adverse effects / Q000494:pharmacology; D010957:Plasmids; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera; D014162:Transfection; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics*
D004268:DNA-Binding Proteins; D006016:Glycolates; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C095888:xeroderma pigmentosum group F protein; D001761:Bleomycin; D004247:DNA; D006861:Hydrogen Peroxide; D004720:Endonucleases; C013193:phosphoglycolate; D010269:Paraquat