The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity.
DNA damage leads to activation of several mechanisms such as DNA repair and cell-cycle checkpoints. It is evident that these different cellular mechanisms have to be finely co-ordinated. Growing evidence suggests that the Rad9/Rad1/Hus1 cell-cycle checkpoint complex (9-1-1 complex), which is recruited to DNA lesion upon DNA damage, plays a major role in DNA repair. This complex has been shown to interact with and stimulate several proteins involved in long-patch base excision repair. On the other hand, the well-characterised DNA clamp-proliferating cell nuclear antigen (PCNA) also interacts with and stimulates several of these factors. In this work, we compared the effects of the 9-1-1 complex and PCNA on flap endonuclease 1 (Fen1). Our data suggest that PCNA and the 9-1-1 complex can independently bind to and activate Fen1. Finally, acetylation of Fen1 by p300-HAT abolished the stimulatory effect of the 9-1-1 complex but not that of PCNA, suggesting a possible mechanism of regulation of this important repair pathway.
Friedrich-Heineken
Erica
E
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
Toueille
Magali
M
Tännler
Barbara
B
Bürki
Christine
C
Ferrari
Elena
E
Hottiger
Michael O
MO
Hübscher
Ulrich
U
D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D003001:Cloning, Molecular; D004249:DNA Damage; D004260:DNA Repair; D005092:Exonucleases / Q000502:physiology; D045585:Flap Endonucleases / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D005092:Exonucleases; D045585:Flap Endonucleases; D051548:Histone Acetyltransferases; D046912:Multiprotein Complexes; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C549605:HUS1 protein, human; C462949:HUS1B protein, human; C069930:rad9 protein; C113574:Rad1 protein, human