PMID- 8756462
OWN - NLM
STAT- MEDLINE
DCOM- 19960918
LR  - 20131121
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 35
IP  - 31
DP  - 1996 Aug 6
TI  - Repair of cisplatin--DNA adducts by the mammalian excision nuclease.
PG  - 10004-13
AB  - Nucleotide excision repair is one of the many cellular defense mechanisms against 
      the toxic effects of cisplatin. An in vitro excision repair assay employing 
      mammalian cell-free extracts was used to determine that the 1,2-d(ApG) 
      intrastrand cross-link, a prevalent cisplatin-DNA adduct, is excised by the 
      excinuclease from a site-specifically modified oligonucleotide 156 base pairs in 
      length. Repair of the minor interstrand d(G)/d(G) cross-link was not detected by 
      using this system. Proteins containing the high mobility group (HMG) domain 
      DNA-binding motif, in particular, rat HMG1 and a murine testis-specific 
      HMG-domain protein, specifically inhibit excision repair of the intrastrand 
      1,2-d(GpG) and -d(ApG) cross-links. This effect was also exhibited by a single 
      HMG domain from HMG1. Similar inhibition of repair of a site-specific 1,2-d(GpG) 
      intrastrand cross-link by an HMG-domain protein also occurred in a reconstituted 
      system containing highly purified repair factors. These results indicate that 
      HMG-domain proteins can block excision repair of the major cisplatin-DNA adducts 
      and suggest that such an activity could contribute to the unique sensitivity of 
      certain tumors to the drug. The reconstituted excinuclease was more efficient at 
      excising the 1,3-d(GpTpG) intrastrand adduct than either the 1,2-d(GpG) or d(ApG) 
      intrastrand adducts, in agreement with previous experiments using whole cell 
      extracts [Huang, J. -C., Zamble, D. B., Reardon, J. T., Lippard, S. J., Sancar, 
      A. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10394-10398]. This result suggests 
      that structural differences among the platinated DNA substrates, and not the 
      presence of unidentified cellular factors, determine the relative excision repair 
      rates of cisplatin-DNA intrastrand cross-links in the whole cell extracts.
FAU - Zamble, D B
AU  - Zamble DB
AD  - Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, 
      USA.
FAU - Mu, D
AU  - Mu D
FAU - Reardon, J T
AU  - Reardon JT
FAU - Sancar, A
AU  - Sancar A
FAU - Lippard, S J
AU  - Lippard SJ
LA  - eng
GR  - CA34992/CA/NCI NIH HHS/United States
GR  - GM32833/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (DNA Adducts)
RN  - 0 (High Mobility Group Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (cisplatin-DNA adduct)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.1.- (Endodeoxyribonucleases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cholesterol/metabolism
MH  - *Cisplatin
MH  - *DNA Adducts
MH  - *DNA Repair
MH  - Endodeoxyribonucleases/*metabolism
MH  - HeLa Cells
MH  - High Mobility Group Proteins/chemistry/metabolism/*pharmacology
MH  - Humans
MH  - Kinetics
MH  - Male
MH  - Mammals
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides
MH  - Rats
MH  - Recombinant Proteins/chemistry/metabolism/pharmacology
MH  - Substrate Specificity
MH  - Testis
EDAT- 1996/08/06 00:00
MHDA- 1996/08/06 00:01
CRDT- 1996/08/06 00:00
PHST- 1996/08/06 00:00 [pubmed]
PHST- 1996/08/06 00:01 [medline]
PHST- 1996/08/06 00:00 [entrez]
AID - bi960453+ [pii]
AID - 10.1021/bi960453+ [doi]
PST - ppublish
SO  - Biochemistry. 1996 Aug 6;35(31):10004-13. doi: 10.1021/bi960453+.