Reactome | Recruitment of the Rad9-Hus1-Rad1 complex to DNA

Recruitment of the Rad9-Hus1-Rad1 complex to DNA

Stable Identifier

R-HSA-176264

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

Recruitment of the 9-1-1 complex to DNA

ReviewStatus

5/5

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Recruitment of the Rad9-Hus1-Rad1 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