3a1j
Crystal structure of the human Rad9-Hus1-Rad1 complex
Structural highlights
FunctionRAD9A_HUMAN Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. RAD9A possesses 3'->5' double stranded DNA exonuclease activity. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThree evolutionarily conserved proteins, Rad9, Hus1, and Rad1, form a heterotrimeric 9-1-1 complex that plays critical roles in cellular responses to DNA damage by activating checkpoints and by recruiting DNA repair enzymes to DNA lesions. We have determined the crystal structure of the human Rad9 (residues 1-272)-Hus1-Rad1 complex at 2.5 A resolution. The 9(1-272)-1-1 complex forms a closed ring, with each subunit having a similar structure. Despite its high level of similarity to proliferating cell nucleus antigen in terms of overall structure, the 9(1-272)-1-1 complex exhibits notable differences in local structures, including interdomain connecting loops, H2 and H3 helices, and loops in the vicinity of the helices of each subunit. These local structural variations provide several unique features to the 9-1-1 heterotrimeric complex-including structures of intermolecular interfaces and the inner surface around the central hole, and different electrostatic potentials at and near the interdomain connecting loops of each 9-1-1 subunit-compared to the proliferating cell nucleus antigen trimer. We propose that these structural features allow the 9-1-1 complex to bind to a damaged DNA during checkpoint control and to serve as a platform for base excision repair. We also show that the 9(1-272)-1-1 complex, but not the full-length 9-1-1 complex, forms a stable complex with the 5' recessed DNA, suggesting that the C-terminal tail of Rad9 is involved in the regulation of the 9-1-1 complex in DNA binding. Crystal structure of the human rad9-hus1-rad1 clamp.,Sohn SY, Cho Y J Mol Biol. 2009 Jul 17;390(3):490-502. Epub 2009 May 21. PMID:19464297[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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