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Titolo:
DNA polymerase eta undergoes alternative splicing, protects against UV sensitivity and apoptosis, and suppresses MreII-dependent recombination
Autore:
Thakur, M; Wernick, M; Collins, C; Limoli, CL; Crowley, E; Cleaver, JE;
Indirizzi:
Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USAUniv Calif San Francisco San Francisco CA USA 94115 ancisco, CA 94115 USA Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
GENES CHROMOSOMES & CANCER
fascicolo: 3, volume: 32, anno: 2001,
pagine: 222 - 235
SICI:
1045-2257(200111)32:3<222:DPEUAS>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
XERODERMA-PIGMENTOSUM VARIANT; ULTRAVIOLET-LIGHT; HUMAN-CELLS; REPLICATION; REPAIR; GENE; DAMAGE; PHOTOPRODUCTS; MUTATIONS; TEMPLATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Cleaver, JE Univ Calif San Francisco, Ctr Comprehens Canc, 2340 Sutter St,Box 0808,Room N-424, San Francisco, CA 94115 USA Univ Calif San Francisco 2340 Sutter St,Box 0808,Room N-424 San Francisco CA USA 94115
Citazione:
M. Thakur et al., "DNA polymerase eta undergoes alternative splicing, protects against UV sensitivity and apoptosis, and suppresses MreII-dependent recombination", GENE CHROM, 32(3), 2001, pp. 222-235

Abstract

Polymerase eta (pot TI) is a low-fidelity DNA polymerase that is the product of the gene, POLH, associated with the human XP variant disorder in which there is an extremely high level of solar-induced skin carcinogenesis. The complete human genomic sequence spans about 40 kb containing 10 coding exons and a cDNA of 2.14 kb; exon 1 is untranslated and is 6 kb upstream fromthe first coding exon. Using bacterial artificial chromosomes (BACs), the gene was mapped to human chromosome band 6p21 and mouse band, 17D. The geneis expressed in most tissues, except for very low or undetectable levels in peripheral lymphocytes, fetal spleen,. and adult muscle; exon II, however, is frequently spliced out in normal cells and in almost half the transcripts in the testis and fetal liver. Expression of POLH in a multicopy episomal vector proved nonviable, suggesting that overexpression is toxic. Expression from chromosomally integrated linear copies using either an EF1-alpha or CMV promoter was functional, resulting in cell lines with low or high levels of pol. il protein, respectively. Point mutations in the center of thegene and in a C-terminal cysteine and deletion of exon II resulted. in inactivation, but addition of a terminal 3 amino acid C-terminal tag, or an N-or C-terminal green fluorescent protein, had no effect on function. A low level of expression of pol eta eliminated hMreII recombination and partially restored UV survival, but did! not prevent UV-induced apoptosis, which required higher levels of expression. Polymerase eta is therefore involved inS-phase checkpoint and signal transduction pathways that lead to. arrest In S, apoptosis, and recombination. In normal cells, the predominant mechanism of replication of UV damage Involves pot eta -dependent bypass, and MreII-dependent recombination that acts is a secondary, backup mechanism when cells are severely depleted of pot eta. (C) 2001 Wiley Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 19:43:48