Poly(ADP-ribose) Polymerase-2 (PARP-2) Is Required for Efficient Base Excision DNA Repair in Association with PARP-1 and XRCC1*

By V. Schreiber, J. Amé, P. Dollé, Inès Schultz, B. Rinaldi, V. Fraulob, J. Ménissier-de murcia, G. de Murcia. Journal of Biological Chemistry, 2002

732 citations recorded by the source corpus.

The DNA damage dependence of poly(ADP-ribose) polymerase-2 (PARP-2) activity is suggestive of its implication in genome surveillance and protection. Here we show that the PARP-2 gene, mainly expressed in actively dividing tissues follows, but to a smaller extent, that of PARP-1 during mouse development. We found that PARP-2 and PARP-1 homo- and heterodimerize; the interacting interfaces, sites of reciprocal modification, have been mapped. PARP-2 was also found to interact with three other proteins involved in the base excision repair pathway: x-ray cross complementing factor 1 (XRCC1), DNA polymerase β, and DNA ligase III, already known as partners of PARP-1. XRCC1 negatively regulates PARP-2 activity, as it does for PARP-1, while being a polymer acceptor for both PARP-1 and PARP-2. To gain insight into the physiological role of PARP-2 in response to genotoxic stress, we developed by gene disruption mice deficient in PARP-2. Following treatment by the alkylating agentN-nitroso-N-methylurea (MNU), PARP-2-deficient cells displayed an important delay in DNA strand breaks resealing, similar to that observed in PARP-1 deficient cells, thus confirming that PARP-2 is also an active player in base excision repair despite its low capacity to synthesize ADP-ribose polymers.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/694db20c074c880e7b7c6ba0dbd8ef5c743ed811

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. W. Kraus
2. Thomas Helleday
3. K. Caldecott
4. B. Kaina
5. W. Roos
6. J. Amé
7. Johan Auwerx
8. R. Houtkooper

In Oncology

1. W. Kraus
2. Johan Auwerx
3. C. Cantó
4. K. Caldecott
5. B. Kaina
6. W. Roos
7. Thomas Helleday
8. Xin Luo

Citations in the corpus

• XRCC1 and DNA strand break repair. (2003, background): “This is supported by the observation that XRCC1 interacts with PARP-1 [48,49], and PARP-2 [38], and that it does so preferentially with autoribosylated PARPs [38,49,50].”
• The PARP Side of the Nucleus: Molecular Actions, Physiological Outcomes, and Clinical Targets (2010, unknown): “These include XRCC-1 in the BER pathway, which requires PARP-1 for its recruitment to sites of DNA damage (El-Khamisy et al., 2003; Heale et al., 2006; Masson et al., 1998; Masson and Caldwell, 1998; Okano et al., 2003).”
• On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. (2012, background): “For example, PARP-1 and PARP-2 can heterodimerize and ADP-ribosylate each other, which may play a role in mediating efficient base excision DNA repair (Schreiber et al. 2002; Menissier de Murcia et al. 2003).”
• Poly(ADP-ribose): novel functions for an old molecule (2006, background): “The inactivation of its gene in mice showed that PARP-2 is required for the maintenance of genomic stability and for the efficient repair of single-stranded DNA lesion”
• The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings (2011, background): “Using this assay, we find that PARP-1 is not required for BER in cells, but rather that the presence of PARP1 protein reduces the BER turnover (Strom et al., 2011).”
• The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. (2008, background): “Moreover PARP1 and PARP2 were proposed to be able to trans-ADP-ribosylate each other at multiple sites, although it is not clear whether the modification is covalent or non-covalent ((136) and own unpublished observations).”
• The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. (2010, background): “PARP2 is the least active one of the two, accounting for only 5–10% of total PARP activity in response to DNA damage (133).”
• The PARP superfamily (2004, background): “Following treatment by the alkylating agent N-nitroso-N-methylurea (MNU), PARP-2-deficient cells displayed a large delay in DNA-strand breaks resealing, similar to that observed in PARP-1-deficient cells,((16)) thus confirming that PARP-2 is an active player in SSBR in spite of its reduced capacity ”
• Mechanisms of human DNA repair: an update. (2003, background): “PARP-2 interacts with XRCC1, Pol␤, and DNA ligase III (Schreiber et al., 2002).”