Recruitment of Rad17-RFC complex to DNA

Stable Identifier
R-HSA-176101
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

The Rad17-RFC complex is involved in an early stage of the genotoxic stress response. The major function of the protein complex is to load the Rad9-Hus1-Rad1 (9-1-1) complex onto DNA at sites of damage and/or stalled replication forks. This reaction is conceptually similar to the loading of the PCNA sliding clamp onto DNA by RFC. The association of the Rad17-RFC complex with ssDNA or gapped or primed DNA is significantly stimulated by RPA, but not by the heterologous E. coli SSB. Loading of the human 9-1-1 complex onto such DNA templates is also strongly stimulated by cognate RPA, but not yeast RPA. Although Rad17 and Rad9 are substrates of the ATR kinase activity, loading of the Rad17 and 9-1-1 complexes onto DNA occurs independent of ATR.

The Rad17-RFC complex is a heteropentamer structurally similar to RFC. The complex contains the four smaller RFC subunits (Rfc2 [p37], Rfc3 [p36], Rfc4 [p40], and Rfc5 [p38]) and the 75 kDa Rad17 subunit in place of the Rfc1 [p140] subunit. The Rad17 complex contains a weak ATPase that is slightly stimulated by primed DNA. Along with binding the 9-1-1 complex and RPA, the Rad17-RFC complex interacts with human MCM7 protein. Each of these interactions is critical for Chk1 activation.

The Rad17 subunit is conserved evolutionarily with the protein showing 49% identity at the amino acid level with the S. pombe rad17 protein. Targeted deletion of the N-terminal region of mouse Rad17 leads to embryonic lethality, strongly suggesting that human Rad17 is also essential for long-term viability.

Rad17-RFC complex associates with DNA substrates containing ssDNA regions including gapped or primed DNA in an ATP-independent reaction. Loading of the Rad9-Hus1-Rad1 (9-1-1) complex occurs preferentially on DNA substrates containing a 5' recessed end. This contrasts with the loading of PCNA by RFC which preferentially occurs on DNA with 3' recessed ends.

Literature References
PubMed ID Title Journal Year
12578958 Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro

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

Proc Natl Acad Sci U S A 2003
14624239 Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA

Ellison, V, Stillman, B

PLoS Biol 2003
14605214 Replication protein A-mediated recruitment and activation of Rad17 complexes

Zou, L, Liu, D, Elledge, SJ

Proc Natl Acad Sci U S A 2003
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