TY - JOUR
T1 - FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair
AU - Unno, Junya
AU - Itaya, Akiko
AU - Taoka, Masato
AU - Sato, Koichi
AU - Tomida, Junya
AU - Sakai, Wataru
AU - Sugasawa, Kaoru
AU - Ishiai, Masamichi
AU - Ikura, Tsuyoshi
AU - Isobe, Toshiaki
AU - Kurumizaka, Hitoshi
AU - Takata, Minoru
PY - 2014/5/22
Y1 - 2014/5/22
N2 - The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.
AB - The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.
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U2 - 10.1016/j.celrep.2014.04.005
DO - 10.1016/j.celrep.2014.04.005
M3 - Article
C2 - 24794430
AN - SCOPUS:84901263371
SN - 2211-1247
VL - 7
SP - 1039
EP - 1047
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -