PMID- 20739229
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20211020
IS  - 1568-7856 (Electronic)
IS  - 1568-7864 (Print)
IS  - 1568-7856 (Linking)
VI  - 9
IP  - 10
DP  - 2010 Oct 5
TI  - The mitochondrial transcription factor A functions in mitochondrial base excision 
      repair.
PG  - 1080-9
LID - 10.1016/j.dnarep.2010.07.009 [doi]
AB  - Mitochondrial transcription factor A (TFAM) is an essential component of 
      mitochondrial nucleoids. TFAM plays an important role in mitochondrial 
      transcription and replication. TFAM has been previously reported to inhibit 
      nucleotide excision repair (NER) in vitro but NER has not yet been detected in 
      mitochondria, whereas base excision repair (BER) has been comprehensively 
      characterized in these organelles. The BER proteins are associated with the inner 
      membrane in mitochondria and thus with the mitochondrial nucleoid, where TFAM is 
      also situated. However, a function for TFAM in BER has not yet been investigated. 
      This study examines the role of TFAM in BER. In vitro studies with purified 
      recombinant TFAM indicate that it preferentially binds to DNA containing 
      8-oxoguanines, but not to abasic sites, uracils, or a gap in the sequence. TFAM 
      inhibited the in vitro incision activity of 8-oxoguanine DNA glycosylase (OGG1), 
      uracil-DNA glycosylase (UDG), apurinic endonuclease 1 (APE1), and nucleotide 
      incorporation by DNA polymerase gamma (pol gamma). On the other hand, a DNA 
      binding-defective TFAM mutant, L58A, showed less inhibition of BER in vitro. 
      Characterization of TFAM knockdown (KD) cells revealed that these lysates had 
      higher 8oxoG incision activity without changes in alphaOGG1 protein levels, TFAM KD 
      cells had mild resistance to menadione and increased damage accumulation in the 
      mtDNA when compared to the control cells. In addition, we found that the tumor 
      suppressor p53, which has been shown to interact with and alter the DNA binding 
      activity of TFAM, alleviates TFAM-induced inhibition of BER proteins. Together, 
      the results suggest that TFAM modulates BER in mitochondria by virtue of its DNA 
      binding activity and protein interactions.
CI  - Published by Elsevier B.V.
FAU - Canugovi, Chandrika
AU  - Canugovi C
AD  - Laboratory of Molecular Gerontology, NIA, National Institutes of Health, 
      Baltimore, MD 21224, United States.
FAU - Maynard, Scott
AU  - Maynard S
FAU - Bayne, Anne-Cecile V
AU  - Bayne AC
FAU - Sykora, Peter
AU  - Sykora P
FAU - Tian, Jingyan
AU  - Tian J
FAU - de Souza-Pinto, Nadja C
AU  - de Souza-Pinto NC
FAU - Croteau, Deborah L
AU  - Croteau DL
FAU - Bohr, Vilhelm A
AU  - Bohr VA
LA  - eng
GR  - Z01 AG000733/ImNIH/Intramural NIH HHS/United States
GR  - Z01-AG000733-14/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20100823
PL  - Netherlands
TA  - DNA Repair (Amst)
JT  - DNA repair
JID - 101139138
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TFAM protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (mitochondrial transcription factor A)
RN  - 5614-64-2 (8-hydroxyguanine)
RN  - 5Z93L87A1R (Guanine)
RN  - EC 2.7.7.7 (DNA Polymerase gamma)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (Uracil-DNA Glycosidase)
RN  - EC 3.2.2.- (oxoguanine glycosylase 1, human)
SB  - IM
MH  - DNA Damage
MH  - DNA Glycosylases/metabolism
MH  - DNA Polymerase gamma
MH  - *DNA Repair
MH  - DNA, Mitochondrial/*metabolism
MH  - DNA-Binding Proteins/*genetics/*metabolism
MH  - DNA-Directed DNA Polymerase/genetics/metabolism
MH  - Guanine/analogs & derivatives/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Mitochondrial Proteins/*genetics/*metabolism
MH  - Oxidative Stress/genetics
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription Factors/*genetics/*metabolism
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Uracil-DNA Glycosidase/genetics/metabolism
PMC - PMC2955416
MID - NIHMS232778
EDAT- 2010/08/27 06:00
MHDA- 2011/01/14 06:00
PMCR- 2011/10/05
CRDT- 2010/08/27 06:00
PHST- 2010/05/01 00:00 [received]
PHST- 2010/07/07 00:00 [revised]
PHST- 2010/07/13 00:00 [accepted]
PHST- 2010/08/27 06:00 [entrez]
PHST- 2010/08/27 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
PHST- 2011/10/05 00:00 [pmc-release]
AID - S1568-7864(10)00239-9 [pii]
AID - 10.1016/j.dnarep.2010.07.009 [doi]
PST - ppublish
SO  - DNA Repair (Amst). 2010 Oct 5;9(10):1080-9. doi: 10.1016/j.dnarep.2010.07.009. 
      Epub 2010 Aug 23.