Biology Reference
In-Depth Information
a PARP inhibitor, so that these patients can benefit from
the low toxicity of these drugs when used alone. In clin-
ical use the majority of anticancer agents are used in
combination, or the targeted agents added to existing
effecting chemotherapy regiments. The ability of PARP
inhibitors to potentiate normal tissue toxicity means
that as these treatment regiments are devised careful
thought needs to be given to scheduling as it might be
necessary to separate cytotoxic drug and PARP inhibitor
treatment to minimize this interaction. However,
patients where PARP inhibitors will be used to enhance
tumor cell kill by a DNA damaging agent (such as radio-
therapy, camptothecins or mono-functional alkylating
agents) concomitant treatment and coverage of enzyme
inhibition for the period when DNA damage is occur-
ring will be necessary.
Although the phase III study of triple negative breast
cancer with iniparib is due to report this year initial indi-
cations are that this study will not meet its primary
objective despite the excellent phase II results, once
again emphasizing the importance of careful preclinial
evaluation of combinations and also mechanism of
action. There also remain many fascinating areas from
translational science for follow-up in clinical develop-
ment
participates in the recognition of single strand breaks on DNA.
J Mol Biol
1989;210(1):229
33.
10. Gradwohl G, Menissier de Murcia JM, Molinete M, Simonin F,
Koken M, Hoeijmakers JH, et al. The second zinc-finger domain
of poly(ADP-ribose) polymerase determines specificity for single-
stranded breaks in DNA.
Proc Natl Acad Sci USA
1990;87(8):
2990
e
4.
11. Langelier MF, Servent KM, Rogers EE, Pascal JM. A third zinc-
binding domain of human poly(ADP-ribose) polymerase-1
coordinates DNA-dependent enzyme activation.
e
J Biol Chem
14.
12. Tao Z, Gao P, Liu HW. Identification of the ADP-ribosylation sites
in the PARP-1 automodification domain: analysis and implica-
tions.
J Am Chem Soc
2009;131(40):14258
2008;283(7):4105
e
60.
13. Altmeyer M, Messner S, Hassa PO, Fey M, Hottiger MO.
Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and
identification of lysine residues as ADP-ribose acceptor sites.
Nucleic Acids Res
2009;37(11):3723
e
38.
14. Cherney BW, McBride OW, Chen DF, Alkhatib H, Bhatia K,
Hensley P, et al. cDNA sequence, protein structure, and chro-
mosomal location of the human gene for poly(ADP-ribose)
polymerase.
Proc Natl Acad Sci USA
1987;84(23):8370
e
4.
15. Simonin F, Menissier-de Murcia J, Poch O, Muller S, Gradwohl G,
Molinete M, et al. Expression and site-directed mutagenesis of
the catalytic domain of human poly(ADP-ribose)polymerase in
Escherichia coli. Lysine 893 is critical for activity.
J Biol Chem
1990;5:19249
e
56.
16. Ruf A, de Murcia G, Schulz GE. Inhibitor and NAD
e
binding to
poly(ADP-ribose) polymerase as derived from crystal structures
and homology modeling.
Biochemistry
1998;37(11):3893
þ
for example the vascular effects of PARP inhib-
itors in terms of tumor drug delivery and also the
research needed to identify a signature of HRD in
sporadic tumors to ensure the right patients are treated
and therefore benefit.
e
900.
17. de Murcia G, Menissier de Murcia J. Poly(ADP-ribose) poly-
merase: a molecular nick-sensor.
Trends Biochem Sci
1994;19(4):
172
e
6.
18. Cleaver JE, Morgan WF. Poly(ADP-ribose)polymerase: a per-
plexing participant in cellular responses to DNA breakage.
Mutat
Res
1991;257(1):1
e
18.
19. Lautier D, Lagueux J, Thibodeau J, Menard L, Poirier GG.
Molecular and biochemical features of poly (ADP-ribose)
metabolism.
Mol Cell Biochem
1993;122(2):171
e
References
93.
20. Mendoza-Alvarez H, Alvarez-Gonzalez R. Poly(ADP-ribose)
polymerase is a catalytic dimer and the automodification reaction
is intermolecular.
J Biol Chem
1993;268:22575
e
1. Chambon P, Weil J, Mandel P. Nicotinamide mononucleotide
activation of a new DNA-dependent polyadenylic acid sythe-
sizing nuclear enzyme.
Biochem Biophys Res Commun
1963;11:39.
2. Sugimura T, Fujimura S, Hasegawa S, Kawamura Y. Polymeri-
zation of the adenosine 5'-diphosphate ribose moiety of NAD
by rat liver nuclear enzyme.
Biochim Biophys Acta
1967;138(2):
438
80.
21. Althaus FR, Hofferer L, Kleczkowska HE, Malanga M, Naegeli H,
Panzeter P, et al. Histone shuttle driven by the automodification
cycle of poly(ADP-ribose)polymerase.
Environ Mol Mutagenesis
1993;22(4):278
e
41.
3. Nishizuka Y, Ueda K, Nakazawa K, Hayaishi O. Studies on the
polymer of adenosine diphosphate ribose. I. Enzymic formation
from nicotinamide adenine dinuclotide in mammalian nuclei.
J Biol Chem
1967;242(13):3164
e
82.
22. Schreiber V, Dantzer F, Ame JC, de Murcia G. Poly(ADP-ribose):
novel functions for an old molecule.
Nature Rev
2006;7(7):517
e
28.
23. Hoeijmakers JH. Genone maintenance mechanisms for prevent-
ing cancer.
Nature
2001;411:360
e
71.
4. Doly J, Petek F. Etude de la structure d-un compose "poly(ADP-
ribose) synthetise par des extraits nucleares de foie de poulet.
CR
Hebd Sciences Acad Sci Ser D Sci Nat
1966;263:1341
e
74.
24. El-Khamisy SF, Masutani M, Suzuki H, Caldecott KW. A
requirement for PARP-1 for the assembly or stability of XRCC1
nuclear foci at sites of oxidative DNA damage.
Nucleic Acids Res
2003;31(19):5526
e
4.
5. Fujimura S. NMN-activated poly(A)polymerase in nuclei from
rat liver and hepatoma cells [in Japanese].
J Japn Biochem Soc
1965;37:584.
6. Chambon P, Weill JD, Doly J, Strosser MT, Mandel P. On the
formation of a novel adencyclic compound by enzymatic extracts
of liver nuclei.
Biochem Biophys Res Commun
1966;25:638
e
33.
25. Davidovic L, Vodenicharov M, Affar EB, Poirier GG. Importance
of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-
ribose) metabolism.
Exp Cell Res
2001;268(1):7
e
13.
26. Oei SL, Ziegler M. ATP for the DNA ligation step in base excision
repair
e
43.
7. Roitt IM. The inhibition of carbohydrate metabolism in ascites-
tumour cells by ethyleneimines.
Biochem J
1956;63(2):300
e
is generated from poly(ADP-ribose).
J Biol Chem
9.
27. Pleschke JM, Kleczkowska HE, Strohm M, Althaus FR.
Poly(ADP-ribose) binds to specific domains in DNA damage
checkpoint proteins.
J Biol Chem
2000;275(52):40974
2000;275(30):23234
7.
8. Auer B, Nagl U, Herzog H, Schneider R, Schweiger M. Human
nuclear NAD
e
e
ADP-ribosyltransferase(polymerizing): organiza-
tion of the gene.
DNA
1989;8(8):575
þ
80.
9. Menissier-de Murcia J, Molinete M, Gradwohl G, Simonin F, de
Murcia G. Zinc-binding domain of poly(ADP-ribose)polymerase
e
80.
28. Benjamin RC, Gill DM. Poly(ADP-ribose) synthesis in vitro pro-
grammed by damaged DNA. A comparison of DNA molecules
e
