Article
RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair
Author/s | Moreno Oñate, Marta
Herrero Ruiz, Andrés M. García Domínguez, Mario Cortés Ledesma, Felipe Ruiz Pérez, José Francisco |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Publication Date | 2020 |
Deposit Date | 2020-04-08 |
Published in |
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Abstract | Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) ... Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells. |
Citation | Moreno Oñate, M., Herrero Ruiz, A.M., García Domínguez, M., Cortés Ledesma, F. y Ruiz Pérez, .F. (2020). RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair. Journal of Molecular Biology, 432 (13), 3965-3979. |
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