Cell cycle checkpoint protein RAD1

Definition:

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. Isoform 1 possesses 3'->5' double stranded DNA exonuclease activity.

References:

[1]. Wensheng Wang, et al. The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1. Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16762-7. [Content Brief]

[2]. A E Parker, et al. A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes an exonuclease. J Biol Chem. 1998 Jul 17;273(29):18332-9. [Content Brief]

[3]. M Rauen, et al. The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9. J Biol Chem. 2000 Sep 22;275(38):29767-71. [Content Brief]

[4]. R L Cai, et al. HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins. J Biol Chem. 2000 Sep 8;275(36):27909-16. [Content Brief]

[5]. Cecilia Cotta-Ramusino, et al. A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science. 2011 Jun 10;332(6035):1313-7. [Content Brief]

[6]. Vladimir P Bermudez, et al. Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1633-8. [Content Brief]

[7]. Ekaterina Smirnova, et al. The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery. Biochem J. 2005 Jul 1;389(Pt 1):13-7. [Content Brief]

[8]. Magali Toueille, et al. The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair. Nucleic Acids Res. 2004 Jun 22;32(11):3316-24. [Content Brief]

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