title: The PIN domain of EXO1 recognizes poly(ADP-ribose) in DNA damage response.
abstract: Following DNA double-strand breaks, poly(ADP-ribose) (PAR) is quickly and heavily synthesized to mediate fast and early recruitment of a number of DNA damage response factors to the sites of DNA lesions and facilitates DNA damage repair. Here, we found that EXO1, an exonuclease for DNA damage repair, is quickly recruited to the sites of DNA damage via PAR-binding. With further dissection of the functional domains of EXO1, we report that the PIN domain of EXO1 recognizes PAR both in vitro and in vivo and the interaction between the PIN domain and PAR is sufficient for the recruitment. We also found that the R93G variant of EXO1, generated by a single nucleotide polymorphism, abolishes the interaction and the early recruitment. Moreover, our study suggests that the PAR-mediated fast recruitment of EXO1 facilities early DNA end resection, the first step of homologous recombination repair. We observed that other PIN domains could also recognize DNA damage-induced PAR. Taken together, our study demonstrates a novel class of PAR-binding module that plays an important role in DNA damage response.
authors.affiliation: College of Life and Environment Sciences, Shanghai Normal University, Guilin Road 100, Shanghai 200234, China Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA fengz@umich.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA Department of Cell Biology, the Third Military Medical University, Chongqing, 400038, China.
authors.forename: Jiazhong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA 91773, USA.
authors.forename: Shih-Hsun
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA 91773, USA.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Bian
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA 91773, USA xyu@coh.org.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051716:Replication Protein A / Q000378:metabolism*
chemical_list: D051716:Replication Protein A; D011064:Poly Adenosine Diphosphate Ribose; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I