The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein.
Exonuclease 1 (EXO-1), a member of the RAD2 family of nucleases, has recently been proposed to function in the genetic pathways of DNA recombination, repair, and replication which are important for genome integrity. Although the role of EXO-1 is not well understood, its 5' to 3'-exonuclease and flap endonuclease activities may cleave intermediates that arise during DNA metabolism. In this study, we provide evidence that the Werner syndrome protein (WRN) physically interacts with human EXO-1 and dramatically stimulates both the exonucleolytic and endonucleolytic incision functions of EXO-1. The functional interaction between WRN and EXO-1 is mediated by a protein domain of WRN which interacts with flap endonuclease 1 (FEN-1). Thus, the genomic instability observed in WRN-/- cells may be at least partially attributed to the lack of interactions between the WRN protein and human nucleases including EXO-1.
Sharma
Sudha
S
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
Sommers
Joshua A
JA
Driscoll
Henry C
HC
Uzdilla
Laura
L
Wilson
Teresa M
TM
Brosh
Robert M
RM
D001665:Binding Sites; D004265:DNA Helicases / Q000737:chemistry / Q000502:physiology*; D045643:DNA Repair Enzymes; D004277:DNA, Single-Stranded / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D045585:Flap Endonucleases; D006801:Humans; D007700:Kinetics; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases; D000071657:Werner Syndrome Helicase
D004277:DNA, Single-Stranded; C114331:EXO1 protein, human; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D045585:Flap Endonucleases; C468317:FEN1 protein, human; C028450:exodeoxyribonuclease I; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D045643:DNA Repair Enzymes