Abstract
The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-Associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork.
| Original language | English |
|---|---|
| Pages (from-to) | 10758-10771 |
| Number of pages | 14 |
| Journal | Nucleic Acids Research |
| Volume | 44 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 2016 Dec 1 |
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ASJC Scopus subject areas
- Genetics
Cite this
FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. / Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi.
In: Nucleic Acids Research, Vol. 44, No. 22, 01.12.2016, p. 10758-10771.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end
AU - Sato, Koichi
AU - Shimomuki, Mayo
AU - Katsuki, Yoko
AU - Takahashi, Daisuke
AU - Kobayashi, Wataru
AU - Ishiai, Masamichi
AU - Miyoshi, Hiroyuki
AU - Takata, Minoru
AU - Kurumizaka, Hitoshi
PY - 2016/12/1
Y1 - 2016/12/1
N2 - The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-Associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork.
AB - The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-Associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork.
UR - http://www.scopus.com/inward/record.url?scp=85016143297&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016143297&partnerID=8YFLogxK
U2 - 10.1093/nar/gkw876
DO - 10.1093/nar/gkw876
M3 - Article
C2 - 27694619
AN - SCOPUS:85016143297
VL - 44
SP - 10758
EP - 10771
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 22
ER -