Recruitment of the 9-1-1 complex to DNA Authored: Borowiec, JA, 2006-02-25 17:40:15 Edited: D'Eustachio, P, 2006-02-25 17:41:28 GENE ONTOLOGYGO:0006260 Pubmed10777662 Pubmed12237462 Pubmed12578958 Pubmed14500360 Pubmed14605214 Pubmed14624239 Pubmed15210332 Pubmed8943031 Reactome Database ID Release 43176264 Reactome, http://www.reactome.org ReactomeREACT_6729 Recruitment of the Rad9-Hus1-Rad1 complex to DNA The 9-1-1 complex is a heterotrimeric ring-shaped structure that is loaded onto DNA by the Rad17-RFC complex. In vitro studies indicate that loading is preferred onto DNA substrates containing ssDNA gaps that presumably resemble structures found upon replication fork stalling and DNA polymerase/helicase uncoupling. The Rad17-RFC and 9-1-1 complexes are structurally similar to the RFC (replication factor C) clamp loader and PCNA sliding clamp, respectively, and similar mechanisms are thought to be used during loading of the 9-1-1 complex and PCNA. Upon loading, the 9-1-1 complex can recruit Chk1 onto sites of replication fork uncoupling or DNA damage.<p>The purified Rad17 and Rad9-Hus1-Rad1 (9-1-1) complexes can form a stable co-complex in the presence of ATP, using Rad17-Rad9 interactions. From computer modeling studies, the Rad17 subunit of the complex is also proposed to interact with the C-terminus of Rad1, p36 with the C-terminus of Hus1, and p38 with the C-terminus of Rad9. A major known function of the 9-1-1 complex is to recruit Chk1 to stalled replication forks for activation by ATR. However, the presence of the 9-1-1 complex also alters the ability of Rad17 to become phosphorylated, perhaps suggesting that 9-1-1 may regulate the recruiment of additional ATR substrates. The 9-1-1 complex has also been found to interact with base excision repair factors human DNA polymerase beta, flap endonuclease FEN1, and the S. pombe MutY homolog (SpMYH), indicating that 9-1-1 also plays a direct role in DNA repair. Rad17-RFC complex bound to DNA Rad9-Hus1-Rad1 bound to DNA 9-1-1 complex