000078245 001__ 78245
000078245 005__ 20200117221628.0
000078245 0247_ $$2doi$$a10.1016/j.biochi.2017.11.013
000078245 0248_ $$2sideral$$a103484
000078245 037__ $$aART-2018-103484
000078245 041__ $$aeng
000078245 100__ $$ade Barros, A.C.
000078245 245__ $$aDNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway
000078245 260__ $$c2018
000078245 5060_ $$aAccess copy available to the general public$$fUnrestricted
000078245 5203_ $$aMLH1 and PMS2 proteins form the MutLa heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLa comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLa is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-a bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-a as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLa heterodimer is discussed.
000078245 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
000078245 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000078245 590__ $$a3.362$$b2018
000078245 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b120 / 294 = 0.408$$c2018$$dQ2$$eT2
000078245 592__ $$a1.277$$b2018
000078245 593__ $$aMedicine (miscellaneous)$$c2018$$dQ1
000078245 593__ $$aBiochemistry$$c2018$$dQ1
000078245 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000078245 700__ $$aTakeda, A.A.S.
000078245 700__ $$aDreyer, T.R.
000078245 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000078245 700__ $$aKobe, B.
000078245 700__ $$aFontes, M.R.M.
000078245 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000078245 773__ $$g146 (2018), 87-96$$pBiochimie$$tBIOCHIMIE$$x0300-9084
000078245 8564_ $$s808738$$uhttps://zaguan.unizar.es/record/78245/files/texto_completo.pdf$$yPostprint
000078245 8564_ $$s7946$$uhttps://zaguan.unizar.es/record/78245/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000078245 909CO $$ooai:zaguan.unizar.es:78245$$particulos$$pdriver
000078245 951__ $$a2020-01-17-21:58:19
000078245 980__ $$aARTICLE