| Structural highlights
Function
MEC3_YEAST Component of the checkpoint clamp complex involved in the surveillance mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes. Associates with sites of DNA damage and modulates the MEC1 signaling pathway and the activation of RAD53 in response to DNA damage at phase G1. The complex also physically regulates DNA polymerase zeta-dependent mutagenesis by controlling the access of polymerase zeta to damaged DNA.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
The 9-1-1 DNA checkpoint clamp is loaded onto 5'-recessed DNA to activate the DNA damage checkpoint that arrests the cell cycle. The 9-1-1 clamp is a heterotrimeric ring that is loaded in Saccharomyces cerevisiae by Rad24-RFC (hRAD17-RFC), an alternate clamp loader in which Rad24 replaces Rfc1 in the RFC1-5 clamp loader of proliferating cell nuclear antigen (PCNA). The 9-1-1 clamp loading mechanism has been a mystery, because, unlike RFC, which loads PCNA onto a 3'-recessed junction, Rad24-RFC loads the 9-1-1 ring onto a 5'-recessed DNA junction. Here we report two cryo-EM structures of Rad24-RFC-DNA with a closed or 27-A open 9-1-1 clamp. The structures reveal a completely unexpected mechanism by which a clamp can be loaded onto DNA. Unlike RFC, which encircles DNA, Rad24 binds 5'-DNA on its surface, not inside the loader, and threads the 3' ssDNA overhang into the 9-1-1 clamp from above the ring.
DNA is loaded through the 9-1-1 DNA checkpoint clamp in the opposite direction of the PCNA clamp.,Zheng F, Georgescu RE, Yao NY, O'Donnell ME, Li H Nat Struct Mol Biol. 2022 Apr;29(4):376-385. doi: 10.1038/s41594-022-00742-6. , Epub 2022 Mar 21. PMID:35314830[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Giannattasio M, Sommariva E, Vercillo R, Lippi-Boncambi F, Liberi G, Foiani M, Plevani P, Muzi-Falconi M. A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12997-3002. PMID:12271137 doi:10.1073/pnas.202463999
- ↑ Majka J, Burgers PM. Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2249-54. Epub 2003 Feb 25. PMID:12604797 doi:https://dx.doi.org/10.1073/pnas.0437148100
- ↑ Giannattasio M, Sabbioneda S, Minuzzo M, Plevani P, Muzi-Falconi M. Correlation between checkpoint activation and in vivo assembly of the yeast checkpoint complex Rad17-Mec3-Ddc1. J Biol Chem. 2003 Jun 20;278(25):22303-8. PMID:12672803 doi:10.1074/jbc.M301260200
- ↑ Majka J, Burgers PM. Function of Rad17/Mec3/Ddc1 and its partial complexes in the DNA damage checkpoint. DNA Repair (Amst). 2005 Sep 28;4(10):1189-94. PMID:16137930 doi:10.1016/j.dnarep.2005.07.008
- ↑ Sabbioneda S, Minesinger BK, Giannattasio M, Plevani P, Muzi-Falconi M, Jinks-Robertson S. The 9-1-1 checkpoint clamp physically interacts with polzeta and is partially required for spontaneous polzeta-dependent mutagenesis in Saccharomyces cerevisiae. J Biol Chem. 2005 Nov 18;280(46):38657-65. PMID:16169844 doi:10.1074/jbc.M507638200
- ↑ Cardone JM, Revers LF, Machado RM, Bonatto D, Brendel M, Henriques JA. Psoralen-sensitive mutant pso9-1 of Saccharomyces cerevisiae contains a mutant allele of the DNA damage checkpoint gene MEC3. DNA Repair (Amst). 2006 Feb 3;5(2):163-71. PMID:16202664 doi:10.1016/j.dnarep.2005.08.018
- ↑ Kondo T, Matsumoto K, Sugimoto K. Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway. Mol Cell Biol. 1999 Feb;19(2):1136-43. PMID:9891048 doi:10.1128/MCB.19.2.1136
- ↑ Corda Y, Schramke V, Longhese MP, Smokvina T, Paciotti V, Brevet V, Gilson E, Geli V. Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions. Nat Genet. 1999 Feb;21(2):204-8. PMID:9988274 doi:https://dx.doi.org/10.1038/5991
- ↑ Zheng F, Georgescu RE, Yao NY, O'Donnell ME, Li H. DNA is loaded through the 9-1-1 DNA checkpoint clamp in the opposite direction of the PCNA clamp. Nat Struct Mol Biol. 2022 Apr;29(4):376-385. PMID:35314830 doi:10.1038/s41594-022-00742-6
|
