Recruitment of the Rad9-Hus1-Rad1 complex to DNA

Stable Identifier
Reaction [transition]
Homo sapiens
Recruitment of the 9-1-1 complex to DNA
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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.

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.

Literature References
PubMed ID Title Journal Year
14500360 Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue

Hopkins, KM, Thaker, HM, Berlin, A, Lieberman, HB, Hang, H, Wang, X

Cancer Res 2003
14624239 Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA

Stillman, B, Ellison, V

PLoS Biol 2003
10777662 Physical interactions among human checkpoint control proteins HUS1p, RAD1p, and RAD9p, and implications for the regulation of cell cycle progression

Lieberman, HB, Hang, H

Genomics 2000
8943031 A human homolog of the Schizosaccharomyces pombe rad9+ checkpoint control gene

Hopkins, KM, Davey, S, Nass, M, Lieberman, HB, Demetrick, D

Proc Natl Acad Sci U S A 1996
12578958 Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro

Lindsey-Boltz, LA, Hurwitz, J, Maniwa, Y, Sancar, A, Cesare, AJ, Bermudez, VP, Griffith, JD

Proc Natl Acad Sci U S A 2003
14605214 Replication protein A-mediated recruitment and activation of Rad17 complexes

Zou, L, Elledge, SJ, Liu, D

Proc Natl Acad Sci U S A 2003
Event Information
Go Biological Process
Catalyst Activity

DNA clamp loader activity of Rad17-RFC complex bound to DNA [nucleoplasm]

Orthologous Events
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