SUMOylation and PARylation cooperate to recruit and stabilize SLX4 at DNA damage sites.
SUMOylation plays important roles in the DNA damage response. However, whether it is important for interstrand crosslink repair remains unknown. We report that the SLX4 nuclease scaffold protein is regulated by SUMOylation. We have identified three SUMO interaction motifs (SIMs) in SLX4, mutating all of which abrogated the binding of SLX4 to SUMO-2 and covalent SLX4 SUMOylation. An SLX4 mutant lacking functional SIMs is not recruited to PML nuclear bodies nor stabilized at laser-induced DNA damage sites. Additionally, we elucidated a novel role for PARylation in the recruitment of SLX4 to sites of DNA damage. Combined, our results uncover how SLX4 is regulated by post-translational modifications.
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands Vertegaal@lumc.nl R.Gonzalez_Prieto@lumc.nl.
Román
R
González-Prieto
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
Sabine A G
SA
Cuijpers
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Martijn S
MS
Luijsterburg
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Haico
H
van Attikum
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands Vertegaal@lumc.nl R.Gonzalez_Prieto@lumc.nl.
Alfred C O
AC
Vertegaal
D001665:Binding Sites; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D021381:Protein Transport; D045522:Recombinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation
D045522:Recombinases; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D004247:DNA; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C542319:SLX4 protein, human
DNA repair; PARP; SLX4; SUMO; ubiquitin