RT Journal Article
SR Electronic
T1 RanBP2-mediated SUMOylation promotes human DNA polymerase lambda nuclear localization and DNA repair
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.14.949644
DO 10.1101/2020.02.14.949644
A1 M. Moreno-Oñate
A1 A.M. Herrero-Ruiz
A1 M. García-Dominguez
A1 F. Cortés-Ledesma
A1 J.F. Ruiz
YR 2020
UL http://biorxiv.org/content/early/2020/02/15/2020.02.14.949644.abstract
AB 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.