Interplay between Np95 and Eme1 in the DNA damage response.
Mus81 (methyl methansulfonate UV sensitive clone 81) and Eme1 (essential meiotic endonuclease 1, also known as MMS4) form a heterodimeric endonuclease that is critical for genomic stability and the response to DNA crosslink damage and replication blockade. However, relatively little is known as to how this endonuclease is regulated following DNA damage. Here, we report mammalian Eme1 interacts with Np95, an E3 ubiquitin ligase that participates in chromatin modification, replication-linked epigenetic maintenance and the DNA damage response. Np95 and Eme1 co-localize on nuclear chromatin following exposure of cells to camptothecin, an agent that promotes the collapse of replication forks. The observed co localization following DNA damage was found to be dependent on an intact RING finger, the structural motif that encodes the E3 ubiquitin ligase activity of Np95. Taken together, these findings link Mus81-Eme1 with the replication-associated chromatin modifier functions of Np95 in the cellular response to DNA damage.
Mistry
Helena
H
Department of Pharmacology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Gibson
Lianne
L
Yun
Ji Weon
JW
Sarras
Haya
H
Tamblyn
Laura
L
McPherson
John Peter
JP
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D054829:RING Finger Domains / Q000235:genetics; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C117054:Uhrf1 protein, mouse; C480534:Eme1 protein, mouse; D004706:Endodeoxyribonucleases