Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
DNA repair inhibitors
Autore:
Berthet, N; Boturyn, D; Constant, JF;
Indirizzi:
Univ Grenoble 1, CNRS, UMR 5616, LEDSS, F-38041 Grenoble 9, France Univ Grenoble 1 Grenoble France 9 616, LEDSS, F-38041 Grenoble 9, France
Titolo Testata:
EXPERT OPINION ON THERAPEUTIC PATENTS
fascicolo: 4, volume: 9, anno: 1999,
pagine: 401 - 415
SICI:
1354-3776(199904)9:4<401:DRI>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEOTIDE EXCISION-REPAIR; HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CLEAVE APURINIC SITES; STRAND BREAK REPAIR; POLY(ADP-RIBOSE) POLYMERASE; IN-VITRO; ANTITUMOR-ACTIVITY; DRUG-RESISTANCE; MISMATCH REPAIR; ABASIC SITE;
Keywords:
alkyl transferase; alkylguanine; DNA repair inhibitors; excision repair; poly(ADP-ribose)polymerase;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
77
Recensione:
Indirizzi per estratti:
Indirizzo: Constant, JF Univ Grenoble 1, CNRS, UMR 5616, LEDSS, BP 53, F-38041 Grenoble 9, France Univ Grenoble 1 BP 53 Grenoble France 9 1 Grenoble 9, France
Citazione:
N. Berthet et al., "DNA repair inhibitors", EXPERT OP T, 9(4), 1999, pp. 401-415

Abstract

DNA repair is essential for cell survival by preventing the formation of mutations which can be lethal and in some cases at the origin of tumours. The DNA repair may occur directly by enzymatic removal of damage from the nucleobase or indirectly, step by step (recognition of the damage, excision, DNA resynthesis). During chemotherapeutic treatment of cancer, the action ofDNA repair proteins may lead to tumour cell resistance. This resistance might be overcome by the use of DNA repair inhibitors. The better characterised repair proteins are O-6 -alkylguanine alkyltransferases (AGT) and poly(ADP-ribose) polymerase (PARP). ACT removes alkylgroups from guanine O-6 position via a one step suicide mechanism. The inhibition of AGT activity results from alkylation of the enzyme with a reactive O-6 modified guanine analogue. Encouraging results were obtained in combination with mono-alkylating agents on cell cultures. O-6-benzylguanine (O-6-BG) has been used in clinical trials. PARP is implicated in single strand break repair (SSB). This enzyme catalyses the formation of branched (ADP-ribose) polymers using NAD as a unique source of nucleotides. Various compounds including nicotinamide and benzamide analogues appeared to inhibit PARP activity in vitro and in cultured cells. Promising results have been obtained with excision repair pathways: base excision repair (BER) and nucleotide excision repair (NER). Recently, gene therapy has been envisaged to introduce DNA repair protein antagonists or p53 protein to trigger apoptosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 06:44:21