PMID- 18171670
OWN - NLM
STAT- MEDLINE
DCOM- 20080512
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 12
DP  - 2008 Mar 21
TI  - Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA 
      double-strand break repair.
PG  - 7713-20
LID - 10.1074/jbc.M710245200 [doi]
AB  - BRCA1 plays an important role in the homologous recombination (HR)-mediated DNA 
      double-strand break (DSB) repair, but the mechanism is not clear. Here we 
      describe that BRCA1 forms a complex with CtIP and MRN (Mre11/Rad50/Nbs1) in a 
      cell cycle-dependent manner. Significantly, the complex formation, especially the 
      ionizing radiation-enhanced association of BRCA1 with MRN, requires 
      cyclin-dependent kinase activity. CtIP directly interacts with Nbs1. The in vivo 
      association of BRCA1 with MRN is largely dependent on the association of CtIP 
      with the BRCT domains at the C terminus of BRCA1, whereas the N terminus of BRCA1 
      also contributes to its association with MRN. CtIP, as well as the interaction of 
      BRCA1 with CtIP and MRN, is critical for IR-induced single-stranded DNA formation 
      and cellular resistance to radiation. Consistently, CtIP itself is required for 
      efficient HR-mediated DSB repair, like BRCA1 and MRN. These studies suggest that 
      the complex formation of BRCA1.CtIP.MRN is important for facilitating DSB 
      resection to generate single-stranded DNA that is needed for HR-mediated DSB 
      repair. Because cyclin-dependent kinase is important for establishing IR-enhanced 
      interaction of MRN with BRCA1, we propose that the cell cycle-dependent complex 
      formation of BRCA1, CtIP, and MRN contributes to the activation of HR-mediated 
      DSB repair in the S and G(2) phases of the cell cycle.
FAU - Chen, Longchuan
AU  - Chen L
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, California 92037, USA.
FAU - Nievera, Christian J
AU  - Nievera CJ
FAU - Lee, Alan Yueh-Luen
AU  - Lee AY
FAU - Wu, Xiaohua
AU  - Wu X
LA  - eng
GR  - CA102361/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080102
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA1 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MRE11 protein, human)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NBN protein, human)
RN  - 0 (Nuclear Proteins)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.1.- (Endodeoxyribonucleases)
RN  - EC 3.1.- (MRE11 Homologue Protein)
RN  - EC 3.1.- (RBBP8 protein, human)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
RN  - EC 3.6.- (RAD50 protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
SB  - IM
MH  - Acid Anhydride Hydrolases
MH  - BRCA1 Protein/genetics/*metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cell Line
MH  - Cyclin-Dependent Kinases/genetics/metabolism
MH  - *DNA Breaks, Double-Stranded/radiation effects
MH  - DNA Repair Enzymes/genetics/metabolism
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Endodeoxyribonucleases
MH  - G2 Phase/*physiology/radiation effects
MH  - Humans
MH  - MRE11 Homologue Protein
MH  - Multiprotein Complexes/genetics/*metabolism
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Protein Structure, Tertiary/genetics
MH  - Radiation, Ionizing
MH  - S Phase/*physiology/radiation effects
EDAT- 2008/01/04 09:00
MHDA- 2008/05/13 09:00
CRDT- 2008/01/04 09:00
PHST- 2008/01/04 09:00 [pubmed]
PHST- 2008/05/13 09:00 [medline]
PHST- 2008/01/04 09:00 [entrez]
AID - S0021-9258(20)55162-4 [pii]
AID - 10.1074/jbc.M710245200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Mar 21;283(12):7713-20. doi: 10.1074/jbc.M710245200. Epub 2008 
      Jan 2.