PMID- 11854176
OWN - NLM
STAT- MEDLINE
DCOM- 20020709
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 11
IP  - 4
DP  - 2002 Feb 15
TI  - Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.
PG  - 439-44
AB  - Fanconi anemia (FA) is a rare genetic disease characterized by chromosome 
      instability, progressive pancytopenia and cancer susceptibility. Telomeres are 
      intimately related to chromosome stability and play an important role in 
      organismal viability at the hematological level. Since previous works suggested 
      an accelerated shortening of telomeres in FA, we have studied several markers of 
      telomere integrity and function in FA patients and age-matched controls to get 
      insights into the mechanisms and consequences of telomere erosion in FA. A higher 
      frequency of extra-chromosomic TTAGGG signals and of chromosome ends with 
      undetectable TTAGGG repeats was observed in FA cells by fluorescence in situ 
      hybridization (FISH), suggesting intensive breakage at telomeric sequences. This 
      was proven by measuring the frequency of excess of telomeric signals per cell, 
      which was 2.8-fold higher in FA. Consistent with previous reports, quantitative 
      FISH analysis showed an accelerated telomere shortening of 0.68 kb in FA, which 
      occurred concurrently in both chromosome arms in a similar magnitude. Our data 
      therefore suggest that the telomere erosion in FA is caused by a higher rate of 
      breakage at TTAGGG sequences in vivo in differentiated cells, in addition to mere 
      replicative shortening during lymphocyte proliferation. Consistent with impaired 
      telomeres in FA patients, we observed a >10-fold increase in chromosome end 
      fusions in FA compared to normal controls. This observation was independent of 
      TRF2, a telomere binding factor that protects human telomeres from end fusions, 
      since immunohistochemistry studies in FA cell lines and corrected counterparts by 
      retrovirus-mediated transfer of FANCA and FANCD2 cDNA showed that a functional FA 
      pathway is not required for telomere binding of TRF2.
FAU - Callen, Elsa
AU  - Callen E
AD  - Group of Mutagenesis, Department of Genetics and Microbiology, Universitat 
      Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
FAU - Samper, Enrique
AU  - Samper E
FAU - Ramirez, Maria J
AU  - Ramirez MJ
FAU - Creus, Amadeu
AU  - Creus A
FAU - Marcos, Ricard
AU  - Marcos R
FAU - Ortega, Juan J
AU  - Ortega JJ
FAU - Olive, Teresa
AU  - Olive T
FAU - Badell, Isabel
AU  - Badell I
FAU - Blasco, Maria A
AU  - Blasco MA
FAU - Surralles, Jordi
AU  - Surralles J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Telomeric Repeat Binding Protein 2)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - DNA-Binding Proteins/metabolism
MH  - Fanconi Anemia/*genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Protein Binding
MH  - *Telomere/pathology
MH  - Telomeric Repeat Binding Protein 2
EDAT- 2002/02/21 10:00
MHDA- 2002/07/10 10:01
CRDT- 2002/02/21 10:00
PHST- 2002/02/21 10:00 [pubmed]
PHST- 2002/07/10 10:01 [medline]
PHST- 2002/02/21 10:00 [entrez]
AID - 10.1093/hmg/11.4.439 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2002 Feb 15;11(4):439-44. doi: 10.1093/hmg/11.4.439.