Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools
Yükleniyor...
Dosyalar
Tarih
2003
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
J Biol Chem
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
The relationship between dNTP levels and DNA synthesis
was investigated using factor-synchronized
yeast treated with the ribonucleotide reductase inhibitor
hydroxyurea (HU). Although HU blocked DNA synthesis
and prevented the dNTP pool expansion that normally
occurs at G1/S, it did not exhaust the levels of any
of the four dNTPs, which dropped to about 80% of G1
levels. When dbf4 yeast that are ts for replication initiation
were allowed to preaccumulate dNTPs at 37 °C
before being released to 25 °C in the presence of HU,
they synthesized 0.3 genome equivalents of DNA and
then arrested as dNTPs approached sub-G1 levels. Accumulation
of dNTPs at G1/S was not a prerequisite for
replication initiation, since dbf4 cells incubated in HU
at 25 °C were able to replicate when subsequently
switched to 37 °C in the absence of HU. The replication
arrest mechanism was not dependent on the Mec1/
Rad53 pathway, since checkpoint-deficient rad53 cells
also failed to exhaust basal dNTPs when incubated in
HU. The persistence of basal dNTP levels in HU-arrested
cells and partial bypass of the arrest in cells that had
preaccumulated dNTPs suggest that cells have a mechanism
for arresting DNA chain elongation when dNTP
levels are not maintained above a critical threshold.
Açıklama
J Biol Chem
Anahtar Kelimeler
Kaynak
J Biol Chem
WoS Q Değeri
Scopus Q Değeri
Cilt
279
Sayı
1
Künye
KOÇ, A., Wheeler, L., Mathews, C., & Gary, M. (2003). Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools . J Biol Chem, (279(1)), 223–0.
