PMID- 10066793
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 11
DP  - 1999 Mar 12
TI  - The topoisomerase-related function gene TRF4 affects cellular sensitivity to the 
      antitumor agent camptothecin.
PG  - 7302-8
AB  - Camptothecin is an antitumor agent that kills cells by converting DNA
      topoisomerase I into a DNA-damaging poison. Although camptothecin derivatives are
      now being used to treat tumors in a variety of clinical protocols, the cellular
      factors that influence sensitivity to the drug are only beginning to be
      understood. We report here that two genes required for sister chromatid cohesion,
      TRF4 and MCD1/SCC1, are also required to repair camptothecin-mediated damage to
      DNA. The hypersensitivity to camptothecin in the trf4 mutant does not result from
      elevated expression of DNA topoisomerase I. We show that Trf4 is a nuclear
      protein whose expression is cell cycle-regulated at a post-transcriptional level.
      Suppression of camptothecin hypersensitivity in the trf4 mutant by gene
      overexpression resulted in the isolation of three genes: another member of the
      TRF4 gene family, TRF5, and two genes that may influence higher order chromosome 
      structure, ZDS1 and ZDS2. We have isolated and sequenced two human TRF4 family
      members, hTRF4-1 and hTRF4-2. The hTRF4-1 gene maps to chromosome 5p15, a region 
      of frequent copy number alteration in several tumor types. The evolutionary
      conservation of TRF4 suggests that it may also influence mammalian cell
      sensitivity to camptothecin.
FAU - Walowsky, C
AU  - Walowsky C
AD  - Department of Microbiology, University of Virginia, Charlottesville, Virginia
      22908, USA.
FAU - Fitzhugh, D J
AU  - Fitzhugh DJ
FAU - Castano, I B
AU  - Castano IB
FAU - Ju, J Y
AU  - Ju JY
FAU - Levin, N A
AU  - Levin NA
FAU - Christman, M F
AU  - Christman MF
LA  - eng
SI  - GENBANK/AF089896
SI  - GENBANK/AF089897
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
RN  - EC 2.7.7.7 (PAP2 protein, S cerevisiae)
RN  - EC 2.7.7.7 (PAPD7 protein, human)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Camptothecin/*pharmacology
MH  - Cell Nucleus/metabolism
MH  - Chromosomal Proteins, Non-Histone/*genetics/metabolism
MH  - Chromosome Mapping
MH  - DNA Repair
MH  - DNA Topoisomerases, Type I/*metabolism
MH  - *DNA-Directed DNA Polymerase
MH  - Enzyme Inhibitors/*pharmacology
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Nuclear Proteins
MH  - Saccharomyces cerevisiae/cytology/drug effects/genetics
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
MH  - Sister Chromatid Exchange
EDAT- 1999/03/06 00:00
MHDA- 1999/03/06 00:01
CRDT- 1999/03/06 00:00
PHST- 1999/03/06 00:00 [pubmed]
PHST- 1999/03/06 00:01 [medline]
PHST- 1999/03/06 00:00 [entrez]
AID - 10.1074/jbc.274.11.7302 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 12;274(11):7302-8. doi: 10.1074/jbc.274.11.7302.