Ubiquitin signaling in the DNA damage response
Attachment of ubiquitin or the ubiquitin-like protein, SUMO, plays a critical role in the response to DNA damage. Monoubiquitin, K63-linked polyubiquitin, K48-linked polyubiquitin and mixed SUMO-ubiquitin chains play distinct roles in signaling DNA damage and recruiting the necessary enzymes needed for DNA repair. We study the enzymes that specifically assemble and disassemble ubiquitin signals at damage sites, as well as the proteins that recognize different types of chains as distinct signals.
Publications
Lombardi PM, Haile S, Rusanov T, Rodell R, Anoh R, Baer JG, Burke KA, Gray LN, Hacker AR, Kebreau KR, Ngandu CK, Orland HA, Osei-Asante E, Schmelyun DP, Shorb DE, Syed SH, Veilleux JM, Majumdar A, Mosammaparast N, Wolberger C. (2022) The ASCC2 CUE domain in the ALKBH3-ASCC DNA repair complex recognizes adjacent ubiquitins in K63-linked polyubiquitin. J Biol Chem. 298(2):101545. doi: 10.1016/j.jbc.2021.101545.
Brickner, Soll , Lombardi , Vågbø , Mudge, Oyeniran, Rabe , Jackson, Sullender, Blazosky, Byrum, Zhao, Corbett, Gécz, Field, Vindigni, Slupphaug, Wolberger, Mosammaparast (2017) A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair. Nature 551: 389-393.
Wiener, DiBello, Lombardi, Guzzo, Zhang, Matunis, Wolberger (2013) E2 ubiquitin-conjugating enzymes regulate the deubiquitinating activity of OTUB1. NSMB 20:1033-9. PubMed
Guzzo, Berndsen, Zhu, Gupta, Datta, Greenberg, Wolberger, Matunis (2012) RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage. Sci Signal. 5(253):ra88. PubMed
Wiener, Zhang, Wang, Wolberger (2012) The mechanism of OTUB1-mediated inhibition of ubiquitination. Nature 483:618-22. PubMed