Journal article
The FANCM/FAAP24 Complex Is Required for the DNA Interstrand Crosslink-Induced Checkpoint Response
Molecular cell, Vol.39(2), pp.259-268
07/30/2010
DOI: 10.1016/j.molcel.2010.07.005
PMCID: PMC2928996
PMID: 20670894
Abstract
Cells from Fanconi anemia (FA) patients are extremely sensitive to DNA interstrand crosslinking (ICL) agents, but the molecular basis of the hypersensitivity remains to be explored. FANCM (FA complementation group M), and its binding partner, FAAP24, anchor the multisubunit FA core complex to chromatin after DNA damage and may contribute to ICL-specific cellular response. Here we show that the FANCM/FAAP24 complex is specifically required for the recruitment of replication protein A (RPA) to ICL-stalled replication forks. ICL-induced RPA foci formation requires the DNA-binding activity of FAAP24 but not the DNA translocase activity of FANCM. Furthermore, FANCM/FAAP24-dependent RPA foci formation is required for efficient ATR-mediated checkpoint activation in response to ICL. Therefore, we propose that FANCM/FAAP24 plays a role in ICL-induced checkpoint activation through regulating RPA recruiment at ICL-stalled replication forks.
Details
- Title: Subtitle
- The FANCM/FAAP24 Complex Is Required for the DNA Interstrand Crosslink-Induced Checkpoint Response
- Creators
- Min Huang - Harvard UniversityJung Min Kim - Harvard UniversityBunsyo Shiotani - Massachusetts General HospitalKailin Yang - Harvard UniversityLee Zou - Harvard UniversityAlan D. D'Andrea - Harvard University
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.39(2), pp.259-268
- Publisher
- Elsevier
- DOI
- 10.1016/j.molcel.2010.07.005
- PMID
- 20670894
- PMCID
- PMC2928996
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Number of pages
- 10
- Grant note
- R01DK043889 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01HL052725 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P01CA092584; RO1DK43889; RO1HL52725 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01CA092584 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 07/30/2010
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696583702771
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