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PMID: 12727891 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse.

The EMBO journal ·Vol. 22 ·No. 9 ·2003-05-01 ·Pages 2255-63

Ménissier de Murcia J, Ricoul M, Tartier L, Niedergang C, Huber A, Dantzer F, Schreiber V, Amé JC, Dierich A, LeMeur M, Sabatier L, Chambon P, de Murcia G

Abstract

The DNA damage-dependent poly(ADP-ribose) polymerases, PARP-1 and PARP-2, homo- and heterodimerize and are both involved in the base excision repair (BER) pathway. Here, we report that mice carrying a targeted disruption of the PARP-2 gene are sensitive to ionizing radiation. Following alkylating agent treatment, parp-2(-/-)-derived mouse embryonic fibroblasts exhibit increased post-replicative genomic instability, G(2)/M accumulation and chromosome mis-segregation accompanying kinetochore defects. Moreover, parp-1(-/-)parp-2(-/-) double mutant mice are not viable and die at the onset of gastrulation, demonstrating that the expression of both PARP-1 and PARP-2 and/or DNA-dependent poly(ADP-ribosyl) ation is essential during early embryogenesis. Interestingly, specific female embryonic lethality is observed in parp-1(+/-)parp-2(-/-) mutants at E9.5. Meta phase analyses of E8.5 embryonic fibroblasts highlight a specific instability of the X chromosome in those females, but not in males. Together, these results support the notion that PARP-1 and PARP-2 possess both overlapping and non-redundant functions in the maintenance of genomic stability.

MeSH Terms
Animals Apoptosis/genetics Base Sequence Chromosomes DNA Damage DNA Primers Embryonic and Fetal Development/physiology Genes, Lethal Isoenzymes/genetics,physiology Methylnitrosourea/pharmacology Mice Mice, Inbred C57BL Mice, Mutant Strains Molecular Sequence Data Poly(ADP-ribose) Polymerases/genetics,physiology Radiation Tolerance
Chemicals
DNA Primers Isoenzymes Methylnitrosourea Poly(ADP-ribose) Polymerases
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Ménissier de Murcia Josiane
Unité 9003 du CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP 10413, 67412 Illkirch Cedex, France.
Ricoul Michelle
Tartier Laurence
Niedergang Claude
Huber Aline
Dantzer Françoise
Schreiber Valérie
Amé Jean-Christophe
Dierich Andrée
LeMeur Marianne
Sabatier Laure
Chambon Pierre
de Murcia Gilbert
References (36)
36 references, click to expand
  1. Accelerated telomere shortening in the human inactive X chromosome.
    Am J Hum Genet. 1999 Dec;65(6):1617-22 PMID: 10577915
  2. Female embryonic lethality in Msh2-Trp53 nullizygous mice is strain dependent.
    Mamm Genome. 1999 Oct;10(10):1020-2 PMID: 10501974
  3. The X chromosome frequently lags behind in female lymphocyte anaphase.
    Am J Hum Genet. 2000 Feb;66(2):687-91 PMID: 10677326
  4. The response of Parp knockout mice against DNA damaging agents.
    Mutat Res. 2000 Apr;462(2-3):159-66 PMID: 10767627
  5. Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1.
    Biochemistry. 2000 Jun 27;39(25):7559-69 PMID: 10858306
  6. Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development.
    Genes Dev. 2000 Aug 15;14(16):2072-84 PMID: 10950870
  7. DNA excision repair and DNA damage-induced apoptosis are linked to Poly(ADP-ribosyl)ation but have different requirements for p53.
    Mol Cell Biol. 2000 Sep;20(18):6695-703 PMID: 10958667
  8. A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability.
    Nat Genet. 2000 Nov;26(3):362-4 PMID: 11062481
  9. X-chromosome inactivation: counting, choice and initiation.
    Nat Rev Genet. 2001 Jan;2(1):59-67 PMID: 11253071
  10. A bidirectional promoter connects the poly(ADP-ribose) polymerase 2 (PARP-2) gene to the gene for RNase P RNA. structure and expression of the mouse PARP-2 gene.
    J Biol Chem. 2001 Apr 6;276(14):11092-9 PMID: 11133988
  11. MACROH2A2, a new member of the MARCOH2A core histone family.
    J Biol Chem. 2001 Jun 15;276(24):21776-84 PMID: 11262398
  12. An unusually compact external promoter for RNA polymerase III transcription of the human H1RNA gene.
    Nucleic Acids Res. 2001 Jun 15;29(12):2502-9 PMID: 11410657
  13. Eukaryotic ribonuclease P: a plurality of ribonucleoprotein enzymes.
    Annu Rev Biochem. 2002;71:165-89 PMID: 12045094
  14. Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1.
    J Biol Chem. 2002 Jun 21;277(25):23028-36 PMID: 11948190
  15. Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated.
    J Biol Chem. 2002 Jul 26;277(30):26921-6 PMID: 12011073
  16. Segregating sister genomes: the molecular biology of chromosome separation.
    Science. 2002 Jul 26;297(5581):559-65 PMID: 12142526
  17. Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc.
    Hum Mol Genet. 2002 Sep 15;11(19):2319-29 PMID: 12217960
  18. Active caspase-8 translocates into the nucleus of apoptotic cells to inactivate poly(ADP-ribose) polymerase-2.
    J Biol Chem. 2002 Sep 13;277(37):34217-22 PMID: 12065591
  19. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors.
    Pharmacol Rev. 2002 Sep;54(3):375-429 PMID: 12223530
  20. A simplified technique for in vivo analysis of sister-chromatid exchanges using 5-bromodeoxyuridine tablets.
    Cytogenet Cell Genet. 1977;18(4):231-7 PMID: 872628
  21. X-chromosome inactivation: molecular mechanisms and genetic consequences.
    Trends Genet. 1994 Jul;10(7):230-5 PMID: 8091502
  22. A subset of p53-deficient embryos exhibit exencephaly.
    Nat Genet. 1995 Jun;10(2):175-80 PMID: 7663512
  23. The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice.
    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8919-23 PMID: 8799128
  24. Activation status of the X chromosome in human micronucleated lymphocytes.
    Hum Genet. 1996 Apr;97(4):471-5 PMID: 8834245
  25. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7303-7 PMID: 9207086
  26. Female embryonic lethality in mice nullizygous for both Msh2 and p53.
    Nat Genet. 1997 Sep;17(1):114-8 PMID: 9288110
  27. PARP is important for genomic stability but dispensable in apoptosis.
    Genes Dev. 1997 Sep 15;11(18):2347-58 PMID: 9308963
  28. DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines.
    Nucleic Acids Res. 1998 Jun 1;26(11):2644-9 PMID: 9592149
  29. Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion.
    Trends Pharmacol Sci. 1998 Jul;19(7):287-98 PMID: 9703762
  30. A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity.
    Mutat Res. 1998 Oct 21;409(1):17-29 PMID: 9806499
  31. Poly(ADP-ribose) polymerase null mouse cells synthesize ADP-ribose polymers.
    J Biol Chem. 1998 Nov 13;273(46):30069-72 PMID: 9804757
  32. Requirement for the Xrcc1 DNA base excision repair gene during early mouse development.
    Dev Biol. 1999 Apr 15;208(2):513-29 PMID: 10191063
  33. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.
    J Biol Chem. 1999 Jun 18;274(25):17860-8 PMID: 10364231
  34. Sister chromatid exchanges are mediated by homologous recombination in vertebrate cells.
    Mol Cell Biol. 1999 Jul;19(7):5166-9 PMID: 10373565
  35. Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7.
    J Biol Chem. 1999 Oct 1;274(40):28379-84 PMID: 10497198
  36. Poly(ADP-ribose) polymerase at active centromeres and neocentromeres at metaphase.
    Hum Mol Genet. 2000 Jan 22;9(2):187-94 PMID: 10607829
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg206
Published
2003-05-01
Pages
2255-63
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156078
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg206 PMC Full Text View journal details
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