| Yazarlar |
Özkan ÖZDEN
Kafkas Üniversitesi, Türkiye |
Faraz Bishehsari
Türkiye |
|
Jessica Bauer
Türkiye |
|
Seonghoon Park
Türkiye |
|
Arundhati Jana
Türkiye |
|
Seung Hyun Baik
Türkiye |
|
Judith Sporn
Türkiye |
|
Jonas J Staudacher
Türkiye |
|
Cemal Yazici
Türkiye |
|
Nancy Krett
Türkiye |
|
Barbara Jung
Türkiye |
| Özet |
| BRCA1-associated RING domain protein 1 (BARD1) stabilizes BRCA1 protein by forming a heterodimeric RING-RING complex, and impacts function of BRCA1, including homologous recombination (HR) repair. Although colon cancer cells usually express wild type BRCA1, presence of an oncogenic BARD1 splice variant (SV) in select cancers may render BRCA1 dysfunctional and allow cells to become sensitive to HR targeting therapies. We previously reported association of loss of full-length (FL) BARD1 with poor prognosis in colon cancer as well as expression of various BARD1 SVs with unknown function. Here we show that loss of BARD1 function through the expression of a BARD1 SV, BARD1β, results in a more malignant phenotype with decreased RAD51 foci formation, reduced BRCA1 E3 ubiquitin ligase activity, and decreased nuclear BRCA1 protein localization. BARD1β sensitizes colon cancer cells to poly ADP ribose polymerase 1 (PARP-1) inhibition even in a FL BRCA1 background. These results suggest that expression of BARD1β may serve as a future biomarker to assess suitability of colon cancers for HR targeting with PARP-1 inhibitors in treatment of advanced colon cancer. |
| Anahtar Kelimeler |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | SCIENTIFIC REPORTS |
| Dergi ISSN | 2045-2322 |
| Dergi Tarandığı Indeksler | SCI |
| Makale Dili | İngilizce |
| Basım Tarihi | 05-2016 |
| Cilt No | 6 |
| Sayfalar | 26273 / 0 |
| Doi Numarası | 10.1038/srep26273 |
| Makale Linki | http://www.nature.com/articles/srep26273 |
| Atıf Sayıları | |
| WoS | 27 |
