title: The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response.
abstract: Poly-ADP-ribosylation is a unique post-translational modification participating in many biological processes, such as DNA damage response. Here, we demonstrate that a set of Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains recognizes poly(ADP-ribose) (PAR) both in vitro and in vivo. Among these FHA and BRCT domains, the FHA domains of APTX and PNKP interact with iso-ADP-ribose, the linkage of PAR, whereas the BRCT domains of Ligase4, XRCC1, and NBS1 recognize ADP-ribose, the basic unit of PAR. The interactions between PAR and the FHA or BRCT domains mediate the relocation of these domain-containing proteins to DNA damage sites and facilitate the DNA damage response. Moreover, the interaction between PAR and the NBS1 BRCT domain is important for the early activation of ATM during DNA damage response and ATM-dependent cell cycle checkpoint activation. Taken together, our results demonstrate two novel PAR-binding modules that play important roles in DNA damage response.
authors: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Mo
authors: M
authors: Li
authors: Lin-Yu
authors: LY
authors: Lu
authors: Chao-Yie
authors: CY
authors: Yang
authors: Shaomeng
authors: S
authors: Wang
authors: Xiaochun
authors: X
authors: Yu
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000378:metabolism; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: C438188:APTX protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; C530380:PNKP protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); D008025:Ligases; D045643:DNA Repair Enzymes
keywords: DNA damage; PAR binding domain; poly(ADP-ribose)
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