Checkpoint deficient rad53 11 yeast cannot accumulate dNTPs in response to DNA damage

Küçük Resim Yok

Tarih

2007

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

Biochem Biophys Res Commun.

Erişim Hakkı

info:eu-repo/semantics/openAccess

Özet

Deoxyribonucleotide pools are maintained at levels that support efficient and yet accurate DNA replication and repair. Rad53 is part of a protein kinase regulatory cascade that, conceptually, promotes dNTP accumulation in four ways: (1) it activates the transcription of ribonucleotide reductase subunits by inhibiting the Crt1 repressor; (2) it plays a role in relocalization of ribonucleotide reductase subunits RNR2 and RNR4 from nucleus to cytoplasm; (3) it antagonizes the action of Sml1, a protein that binds and inhibits ribonucleotide reductase; and (4) it blocks cell-cycle progression in response to DNA damage, thus preventing dNTP consumption through replication forks. Although several lines of evidence support the above modes of Rad53 action, an effect of a rad53 mutation on dNTP levels has not been directly demonstrated. In fact, in a previous study, a rad53-11 mutation did not result in lower dNTP levels in asynchronous cells or in synchronized cells that entered the S-phase in the presence of the RNR inhibitor hydroxyurea. These anomalies prompted us to investigate whether the rad53-11 mutation affected dNTP levels in cells exposed to a DNA-damaging dose of ethylmethyl sulfonate (EMS). Although dNTP levels increased by 2- to 3-fold in EMS treated wild-type cells, rad53-11 cells showed no such change. Thus, the results indicate that Rad53 checkpoint function is not required for dNTP pool maintenance in normally growing cells, but is required for dNTP pool expansion in cells exposed to DNA-damaging agents. 2006 Elsevier Inc. All rights reserved.

Açıklama

Biochem Biophys Res Commun.

Anahtar Kelimeler

Rad53, dNTP, DNA damage, RNR, EMS, Yeast

Kaynak

Biochem Biophys Res Commun.

WoS Q Değeri

Scopus Q Değeri

Cilt

352

Sayı

2

Künye

Koç, A., & Gary, Merrill. (2007). Checkpoint Deficient Rad53 11 Yeast Cannot Accumulate Dntps İn Response To Dna Damage . Biochem Biophys Res Commun., (353 (2)), 527–0.