Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

Autor: Sascha Emilie Liberti, Vilhelm A. Bohr, Lene Juel Rasmussen, Guido Keijzers, Jean-Baptiste Charbonnier, Mylène Perderiset, Finn Cilius Nielsen, Jing Wang, Sofie Dabros Andersen, Alfred May, Simona Miron
Přispěvatelé: Center for Healthy Aging [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Roskilde University, National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Imagerie intégrative de la molécule à l'organisme, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Department of Clinical Biochemistry [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Rok vydání: 2011
Předmět:
DNA Replication
Werner Syndrome Helicase
DNA repair
Recombinant Fusion Proteins
DNA mismatch repair
DNA polymerase II
Amino Acid Motifs
Replication foci
Biology
Biochemistry
DNA polymerase delta
Article
Double strand break
S Phase
Mice
03 medical and health sciences
0302 clinical medicine
Replication factor C
Proliferating Cell Nuclear Antigen
Animals
Humans
DNA Breaks
Double-Stranded
Molecular Biology
Replication protein A
Adaptor Proteins
Signal Transducing
030304 developmental biology
0303 health sciences
DNA clamp
RecQ Helicases
Lasers
hEXO1PCNA
DNA replication
Nuclear Proteins
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
DNA
Cell Biology
Molecular biology
DNA-Binding Proteins
Protein Transport
DNA Repair Enzymes
Exodeoxyribonucleases
Amino Acid Substitution
030220 oncology & carcinogenesis
MutS Homolog 3 Protein
NIH 3T3 Cells
biology.protein
MutL Protein Homolog 1
HeLa Cells
Zdroj: DNA Repair
DNA Repair, 2011, 10, pp.73-86. ⟨10.1016/j.dnarep.2010.09.023⟩
DNA Repair, Elsevier, 2011, 10, pp.73-86. ⟨10.1016/j.dnarep.2010.09.023⟩
ISSN: 1568-7864
Popis: Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues 390-490 and 787-846) are required to direct the protein to the DNA damage site. Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells.
Databáze: OpenAIRE
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