PMID- 16951172
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20190406
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 17
DP  - 2006 Sep 1
TI  - DNA damage binding protein component DDB1 participates in nucleotide excision 
      repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity.
PG  - 8590-7
AB  - Functional defect in DNA damage binding (DDB) activity has a direct relationship 
      to decreased nucleotide excision repair (NER) and increased susceptibility to 
      cancer. DDB forms a complex with cullin 4A (Cul4A), which is now known to 
      ubiquitylate DDB2, XPC, and histone H2A. However, the exact role of DDB1 in NER 
      is unclear. In this study, we show that DDB1 knockdown in human cells impaired 
      their ability to efficiently repair UV-induced cyclobutane pyrimidine dimers 
      (CPD) but not 6-4 photoproducts (6-4PP). Extensive nuclear protein fractionation 
      and chromatin association analysis revealed that upon irradiation, DDB1 protein 
      is translocated from a loosely bound to a tightly bound in vivo chromatin 
      fraction and the DDB1 translocation required the participation of functional DDB2 
      protein. DDB1 knockdown also affected the translocation of Cul4A component to the 
      tightly bound form in UV-damaged chromatin in vivo as well as its recruitment to 
      the locally damaged nuclear foci in situ. However, DDB1 knockdown had no effect 
      on DNA damage binding capacity of DDB2. The data indicated that DDB2 can bind to 
      damaged DNA in vivo as a monomer, whereas Cul4A recruitment to damage sites 
      depends on the fully assembled complex. Our data also showed that DDB1 is 
      required for the UV-induced DDB2 ubiquitylation and degradation. In summary, the 
      results suggest that (a) DDB1 is critical for efficient NER of CPD; (b) DDB1 acts 
      in bridging DDB2 and ubiquitin ligase Cul4A; and (c) DDB1 aids in recruiting the 
      ubiquitin ligase activity to the damaged sites for successful commencement of 
      lesion processing by NER.
FAU - Li, Jinyou
AU  - Li J
AD  - Department of Radiology, The Ohio State University, Columbus, Ohio 43240, USA.
FAU - Wang, Qi-En
AU  - Wang QE
FAU - Zhu, Qianzheng
AU  - Zhu Q
FAU - El-Mahdy, Mohamed A
AU  - El-Mahdy MA
FAU - Wani, Gulzar
AU  - Wani G
FAU - Praetorius-Ibba, Mette
AU  - Praetorius-Ibba M
FAU - Wani, Altaf A
AU  - Wani AA
LA  - eng
GR  - R01 ES012991/ES/NIEHS NIH HHS/United States
GR  - CA93413/CA/NCI NIH HHS/United States
GR  - ES2388/ES/NIEHS NIH HHS/United States
GR  - ES12991/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (DDB1 protein, human)
RN  - 0 (DDB2 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Gentamicins)
RN  - 0 (Recombinant Proteins)
RN  - A08F5XTI6G (antibiotic G 418)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Cullin Proteins/*metabolism
MH  - *DNA Damage
MH  - DNA Repair/*genetics
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Fibroblasts/drug effects/*physiology/radiation effects
MH  - Gentamicins/pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Recombinant Proteins/metabolism
MH  - Transfection
MH  - Ubiquitin-Protein Ligases/*metabolism
MH  - Ultraviolet Rays
EDAT- 2006/09/05 09:00
MHDA- 2007/12/06 09:00
CRDT- 2006/09/05 09:00
PHST- 2006/09/05 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2006/09/05 09:00 [entrez]
AID - 66/17/8590 [pii]
AID - 10.1158/0008-5472.CAN-06-1115 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Sep 1;66(17):8590-7. doi: 10.1158/0008-5472.CAN-06-1115.