Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM
- PMID: 17289582
- DOI: 10.1016/j.molcel.2007.01.003
Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM
Abstract
The Fanconi anemia (FA) core complex plays a crucial role in a DNA damage response network with BRCA1 and BRCA2. How this complex interacts with damaged DNA is unknown, as only the FA core protein FANCM (the homolog of an archaeal helicase/nuclease known as HEF) exhibits DNA binding activity. Here, we describe the identification of FAAP24, a protein that targets FANCM to structures that mimic intermediates formed during the replication/repair of damaged DNA. FAAP24 shares homology with the XPF family of flap/fork endonucleases, associates with the C-terminal region of FANCM, and is a component of the FA core complex. FAAP24 is required for normal levels of FANCD2 monoubiquitylation following DNA damage. Depletion of FAAP24 by siRNA results in cellular hypersensitivity to DNA crosslinking agents and chromosomal instability. Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA.
Comment in
-
The Fanconi anemia signalosome anchor.Mol Cell. 2007 Feb 23;25(4):487-90. doi: 10.1016/j.molcel.2007.02.002. Mol Cell. 2007. PMID: 17317622
Similar articles
-
Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24.Blood. 2008 May 15;111(10):5215-22. doi: 10.1182/blood-2007-09-113092. Epub 2008 Jan 3. Blood. 2008. PMID: 18174376 Free PMC article.
-
FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA.Mutat Res. 2009 Jul 31;668(1-2):20-6. doi: 10.1016/j.mrfmmm.2009.04.002. Epub 2009 Apr 18. Mutat Res. 2009. PMID: 19379763 Free PMC article. Review.
-
Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair.Nucleic Acids Res. 2013 Dec;41(22):10573-83. doi: 10.1093/nar/gkt788. Epub 2013 Sep 3. Nucleic Acids Res. 2013. PMID: 24003026 Free PMC article.
-
Architecture and DNA recognition elements of the Fanconi anemia FANCM-FAAP24 complex.Structure. 2013 Sep 3;21(9):1648-58. doi: 10.1016/j.str.2013.07.006. Epub 2013 Aug 8. Structure. 2013. PMID: 23932590 Free PMC article.
-
Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights.Mutat Res. 2009 Jul 31;668(1-2):54-72. doi: 10.1016/j.mrfmmm.2009.02.003. Epub 2009 Feb 21. Mutat Res. 2009. PMID: 19622404 Free PMC article. Review.
Cited by
-
Biochemical Activities and Genetic Functions of the Drosophila melanogaster Fancm Helicase in DNA Repair.Genetics. 2016 Oct;204(2):531-541. doi: 10.1534/genetics.116.192534. Epub 2016 Jul 27. Genetics. 2016. PMID: 27466228 Free PMC article.
-
ERCC1 and MUS81-EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis.Nat Cell Biol. 2013 Aug;15(8):1008-15. doi: 10.1038/ncb2793. Epub 2013 Jun 30. Nat Cell Biol. 2013. PMID: 23811686
-
AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.Hum Mol Genet. 2015 Sep 15;24(18):5093-108. doi: 10.1093/hmg/ddv227. Epub 2015 Jun 17. Hum Mol Genet. 2015. PMID: 26085575 Free PMC article.
-
FAVL elevation in human tumors disrupts Fanconi anemia pathway signaling and promotes genomic instability and tumor growth.J Clin Invest. 2010 May;120(5):1524-34. doi: 10.1172/JCI40908. Epub 2010 Apr 19. J Clin Invest. 2010. PMID: 20407210 Free PMC article.
-
Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.Cell. 2010 Jul 9;142(1):65-76. doi: 10.1016/j.cell.2010.06.021. Cell. 2010. PMID: 20603015 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous