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Identification of FAAP24, a Fanconi Anemia Core Complex Protein that Interacts with FANCM

Authors :
Yutong Xue
Stephen C. West
El Houari Laghmani
Alberto Ciccia
Chen Ling
Rachel Coulthard
Amom Ruhikanta Meetei
Neil Q. McDonald
Weidong Wang
Hans Joenje
Zhijiang Yan
Johan P. de Winter
Source :
Molecular Cell. 25:331-343
Publication Year :
2007
Publisher :
Elsevier BV, 2007.

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.

Details

ISSN :
10972765
Volume :
25
Database :
OpenAIRE
Journal :
Molecular Cell
Accession number :
edsair.doi.dedup.....a68ec4ff32d8ba7ce0c365e79cba20aa
Full Text :
https://doi.org/10.1016/j.molcel.2007.01.003