PMID- 19129235
OWN - NLM
STAT- MEDLINE
DCOM- 20090417
LR  - 20211203
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 37
IP  - 6
DP  - 2009 Apr
TI  - A role for monoubiquitinated FANCD2 at telomeres in ALT cells.
PG  - 1740-54
LID - 10.1093/nar/gkn995 [doi]
AB  - Both Fanconi anemia (FA) and telomere dysfunction are associated with chromosome 
      instability and an increased risk of cancer. Because of these similarities, we 
      have investigated whether there is a relationship between the FA protein, FANCD2 
      and telomeres. We find that FANCD2 nuclear foci colocalize with telomeres and PML 
      bodies in immortalized telomerase-negative cells. These cells maintain telomeres 
      by alternative lengthening of telomeres (ALT). In contrast, FANCD2 does not 
      colocalize with telomeres or PML bodies in cells which express telomerase. Using 
      a siRNA approach we find that FANCA and FANCL, which are components of the FA 
      nuclear core complex, regulate FANCD2 monoubiquitination and the telomeric 
      localization of FANCD2 in ALT cells. Transient depletion of FANCD2, or FANCA, 
      results in a dramatic loss of detectable telomeres in ALT cells but not in 
      telomerase-expressing cells. Furthermore, telomere loss following depletion of 
      these proteins in ALT cells is associated with decreased homologous recombination 
      between telomeres (T-SCE). Thus, the FA pathway has a novel function in ALT 
      telomere maintenance related to DNA repair. ALT telomere maintenance is therefore 
      one mechanism by which monoubiquitinated FANCD2 may promote genetic stability.
FAU - Fan, Qiang
AU  - Fan Q
AD  - Division of Experimental Hematology and Cancer Biology, Cincinnati Children's 
      Research Foundation, Department of Pediatrics, University of Cincinnati College 
      of Medicine, Cincinnati, OH 45229, USA.
FAU - Zhang, Fan
AU  - Zhang F
FAU - Barrett, Briana
AU  - Barrett B
FAU - Ren, Keqin
AU  - Ren K
FAU - Andreassen, Paul R
AU  - Andreassen PR
LA  - eng
GR  - R01 HL085587/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090107
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Fanconi Anemia Complementation Group A Protein)
RN  - 0 (Fanconi Anemia Complementation Group D2 Protein)
RN  - 0 (Telomeric Repeat Binding Protein 1)
RN  - EC 2.3.2.27 (Fanconi Anemia Complementation Group L Protein)
RN  - EC 2.7.11.1 (ATR protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle Proteins/physiology
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Fanconi Anemia Complementation Group A Protein/antagonists & 
      inhibitors/physiology
MH  - Fanconi Anemia Complementation Group D2 Protein/analysis/antagonists & 
      inhibitors/*metabolism
MH  - Fanconi Anemia Complementation Group L Protein/physiology
MH  - HeLa Cells
MH  - Humans
MH  - Protein Serine-Threonine Kinases/physiology
MH  - Sister Chromatid Exchange
MH  - Telomere/chemistry/*metabolism
MH  - Telomeric Repeat Binding Protein 1/analysis
MH  - *Ubiquitination
PMC - PMC2665210
EDAT- 2009/01/09 09:00
MHDA- 2009/04/18 09:00
PMCR- 2009/01/07
CRDT- 2009/01/09 09:00
PHST- 2009/01/09 09:00 [entrez]
PHST- 2009/01/09 09:00 [pubmed]
PHST- 2009/04/18 09:00 [medline]
PHST- 2009/01/07 00:00 [pmc-release]
AID - gkn995 [pii]
AID - 10.1093/nar/gkn995 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2009 Apr;37(6):1740-54. doi: 10.1093/nar/gkn995. Epub 2009 Jan 
      7.