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Cyclin A2 as a regulator of DNA strand stability (1047.6)
Author(s) -
Gygli Patrick,
Catacutan Fay,
Gokozan Hamza,
Schmidt Theresa,
Stephens Julie,
Palanichamy Kamalakannan,
Otero Jose
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1047.6
Subject(s) - cyclin a , cyclin a2 , rad51 , cyclin , cyclin b1 , cyclin d , biology , cyclin b , homologous recombination , microbiology and biotechnology , cyclin e , cell cycle , cancer research , dna repair , cyclin dependent kinase 1 , dna , genetics , cell
Cyclin A2 regulates replication origin firing during S‐phase. It binds to Cdk1 and Cdk2 to direct phosphorylation of proteins for DNA synthesis. The goals of this study were to determine the role of Cyclin A2 in the prevention of DNA double strand breaks (DSB). We deleted Cyclin A2 in mouse neural stem cells (NSC) using a cre/lox approach. Cyclin A2‐null NSC showed increased BrdU incorporation, as well as increased staining for the mitotic marker pH3. However, the growth rate in these Cyclin A2‐null cells was slowed. To explain this discordance, we examined the DSB marker γH2AX. Cyclin A2‐null NSC show increased levels of γH2AX as compared to Cyclin A2‐preserved cells. When a DSB forms, the cell cycle is arrested until the break is repaired. Rad51, a marker of homologous recombination repair, and 53BP1, a marker of non‐homologous end joining, both localized to the site of DSB in Cyclin A2‐null cells. This indicates that Cyclin A2‐null NSC can repair these breaks. Our results suggest that Cyclin A2 does not function in the repair of DSB, but instead plays a role in DNA strand stability. Because NSC display similarities to glioma initiating cells, our results may be applied to development of a treatment of glioblastoma, which is currently treated by a combination of temozolomide and radiation. Novel therapies for this fatal brain tumor are needed, and Cyclin A2 is a potential target for radiosensitizing therapy for glioblastoma. Grant Funding Source : 1R21EB017539‐01A1, 8UL1TR000090‐05