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Titolo:
UV-induced hyperphosphorylation of replication protein a depends on DNA replication and expression of ATM protein
Autore:
Oakley, GG; Loberg, LI; Yao, JQ; Risinger, MA; Yunker, RL; Zernik-Kobak, M; Khanna, KK; Lavin, MF; Carty, MP; Dixon, K;
Indirizzi:
Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA Univ Cincinnati Cincinnati OH USA 45267 nm Hlth, Cincinnati, OH 45267 USA PO Royal Brisbane Hosp, Bancroft Ctr, Queensland Inst Med Res, Brisbane, Qld, Australia PO Royal Brisbane Hosp Brisbane Qld Australia , Brisbane, Qld, Australia
Titolo Testata:
MOLECULAR BIOLOGY OF THE CELL
fascicolo: 5, volume: 12, anno: 2001,
pagine: 1199 - 1213
SICI:
1059-1524(200105)12:5<1199:UHORPA>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINGLE-STRANDED-DNA; NUCLEOTIDE EXCISION-REPAIR; S-PHASE CHECKPOINT; CHROMOSOMAL ABERRATION PRODUCTION; IRRADIATED HUMAN-FIBROBLASTS; DAMAGE RESPONSE PATHWAYS; ATAXIA-TELANGIECTASIA; BINDING-PROTEIN; IONIZING-RADIATION; P34 SUBUNIT;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
98
Recensione:
Indirizzi per estratti:
Indirizzo: Dixon, K Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA Univ Cincinnati Cincinnati OH USA 45267 Cincinnati, OH 45267 USA
Citazione:
G.G. Oakley et al., "UV-induced hyperphosphorylation of replication protein a depends on DNA replication and expression of ATM protein", MOL BIOL CE, 12(5), 2001, pp. 1199-1213

Abstract

Exposure to DNA-damaging agents triggers signal transduction pathways thatare thought to play a role in maintenance of genomic stability. A key protein in the cellular processes of nucleotide excision repair, DNA recombination, and DNA double-strand break repair is the single-stranded DNA binding protein, RPA. We showed previously that the p34 subunit of RPA becomes hyperphosphorylated as a delayed response (4-8 h) to UV radiation (10-30 J/m(2)). Here we show that UV-induced RPA-p34 hyperphosphorylation depends on expression of ATM, the product of the gene mutated in the human genetic disorder ataxia telangiectasia (A-T). UV-induced RPA-p34 hyperphosphorylation wasnot observed in A-T cells, but this response was restored by ATM expression. Furthermore, purified ATM kinase phosphorylates the p34 subunit of RPA complex in vitro at many of the same sites that are phosphorylated in vivo after UV radiation. Induction of this DNA damage response was also dependenton DNA replication; inhibition of DNA replication by aphidicolin preventedinduction of RPA-p34 hyperphosphorylation by UV radiation. We postulate that this pathway is triggered by the accumulation of aberrant DNA replication intermediates, resulting from DNA replication fork blockage by UV photoproducts. Further, we suggest that RPA-p34 is hyperphosphorylated as a participant in the recombinational postreplication repair of these replication products. Successful resolution of these replication intermediates reduces the accumulation of chromosomal aberrations that would otherwise occur as a consequence of UV radiation.

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Documento generato il 19/09/20 alle ore 17:35:55