Evidence for the involvement of Puralpha in response to DNA replication stress.
Puralpha is a sequence-specific nucleic acid binding protein that is involved in multiple cellular functions including regulation of transcription, initiation of DNA replication, cell cycle progression, and neuronal cell differentiation. Its potential role in DNA repair has not been explored. We have now analyzed the role of Puralpha in the cellular response to replication-associated DNA repair of double-strand breaks (DSBs) using Puralpha knockout mouse embryo fibroblasts (MEFs). We found that Puralpha negative cells are hypersensitive to the DNA replication inhibitor, hydroxyurea (HU), and that HU induces excessive DSBs, which delayed the resumption of cell cycle progression after HU treatment. Reintroduction of Pura into Pura null cells reduced the accumulation of DSBs and enhanced DNA end joining. These results suggest a role for Puralpha as a caretaker protein that is involved in the repair of DSBs induced by stalled replication forks.
Wang
Huichen
H
Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA.
Wang
Meijuan
M
Reiss
Krzysztof
K
Darbinian-Sarkissian
Nune
N
Johnson
Edward M
EM
Iliakis
George
G
Amini
Shohreh
S
Khalili
Kamel
K
Rappaport
Jay
J
D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C121485:Pura protein, mouse; D034741:RNA, Small Interfering; D006918:Hydroxyurea