PARP1 is a TRF2-associated poly(ADP-ribose) polymerase and protects eroded telomeres
Journal Article
·
· Molecular Biology of the Cell
- ORNL
Poly(ADP-ribose)polymerase 1 (PARP1) is well characterized for its role in base excision repair (BER), where it is activated by and binds to DNA breaks and catalyzes the poly(ADP-ribosyl)ation of several substrates involved in DNA damage repair. Here we demonstrate that PARP1 associates with telomere repeat binding factor 2 (TRF2) and is capable of poly(ADP-ribosyl)ation of TRF2, which affects binding of TRF2 to telomeric DNA. Immunostaining of interphase cells or metaphase spreads shows that PARP1 is detected sporadically at normal telomeres, but it appears preferentially at eroded telomeres caused by telomerase deficiency or damaged telomeres induced by DNA-damaging reagents. Although PARP1 is dispensable in the capping of normal telomeres, Parp1 deficiency leads to an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA in primary murine cells after induction of DNA damage. Our results suggest that upon DNA damage, PARP1 is recruited to damaged telomeres, where it can help protect telomeres against chromosome end-to-end fusions and genomic instability.
- Research Organization:
- Oak Ridge National Laboratory (ORNL); Mouse Genetics Research Facility
- Sponsoring Organization:
- ORNL LDRD Seed-Money; ORNL LDRD Director's R&D; SC USDOE - Office of Science (SC)
- DOE Contract Number:
- AC05-00OR22725
- OSTI ID:
- 978248
- Journal Information:
- Molecular Biology of the Cell, Journal Name: Molecular Biology of the Cell Journal Issue: 4 Vol. 17
- Country of Publication:
- United States
- Language:
- English
Similar Records
PARP1 Is a TRF2-associated Poly(ADP-Ribose)Polymerase and Protects Eroded Telomeres
Poly(ADP-ribose) and the response of cells to ionizing radiation
PARP1 Val762Ala polymorphism reduces enzymatic activity
Journal Article
·
Sat Dec 31 23:00:00 EST 2005
· Molecular Biology of the Cell
·
OSTI ID:978186
Poly(ADP-ribose) and the response of cells to ionizing radiation
Conference
·
Mon Dec 31 23:00:00 EST 1984
· Radiat. Res.; (United States)
·
OSTI ID:5930562
PARP1 Val762Ala polymorphism reduces enzymatic activity
Journal Article
·
Thu Mar 01 23:00:00 EST 2007
· Biochemical and Biophysical Research Communications
·
OSTI ID:20979814