@article{594370955c2a480da921972b9f85d50f,
title = "The E3 ligase RFWD3 stabilizes ORC in a p53-dependent manner",
abstract = "RFWD3 is an E3 ubiquitin ligase that plays important roles in DNA damage response and DNA replication. We have previously demonstrated that the stabilization of RFWD3 by PCNA at the replication fork enables ubiquitination of the single-stranded binding protein, RPA and its subsequent degradation for replication progression. Here, we report that RFWD3 associates with the Origin Recognition Complex (ORC) and ORC-Associated (ORCA/LRWD1), components of the pre-replicative complex required for the initiation of DNA replication. Overexpression of ORC/ORCA leads to the stabilization of RFWD3. Interestingly, RFWD3 seems to stabilize ORC/ORCA in cells expressing wild type p53, as the depletion of RFWD3 reduces the levels of ORC/ORCA. Further, the catalytic activity of RFWD3 is required for the stabilization of ORC. Our results indicate that the RFWD3 promotes the stability of ORC, enabling efficient pre-RC assembly.",
keywords = "ORC, ORCA/LRWD1, p53, replication, RFWD3, ubiquitination",
author = "Hsu, {Rosaline Y.C.} and Sumanprava Giri and Yating Wang and Lin, {Yo Chuen} and Dazhen Liu and Susan Wopat and Arindam Chakraborty and Prasanth, {Kannanganattu V.} and Prasanth, {Supriya Gangadharan}",
note = "Funding Information: We thank members of the Prasanth laboratory for discussions and suggestions. We thank Drs. J. Chen, A. Gambus, Z. Gong, A. Mar{\'e}chal, K. Sato, D. Spector, B. Stillman, M. Takata, Y. Wang, and L. Zou for providing reagents, protocols, and suggestions. This work was supported by NSF-CMMB-IGERT fellowship to RH; Cancer center at Illinois seed grant and Prairie Dragon Paddlers and NSF EAGER awards and NIH (GM132458 and AG065748) to KVP; and NSF (1243372 and 1818286) and NIH (GM125196) awards to SGP. The authors declare no competing financial interests. Funding Information: This work was supported by the National Institutes of Health [GM125196; AG065748]; National Institutes of Health [GM132458]; National Science Foundation [1243372]; National Science Foundation [1818286]; National Science Foundation [1723008]. We thank members of the Prasanth laboratory for discussions and suggestions. We thank Drs. J. Chen, A. Gambus, Z. Gong, A. Mar?chal, K. Sato, D. Spector, B. Stillman, M. Takata, Y. Wang, and L. Zou for providing reagents, protocols, and suggestions. This work was supported by NSF-CMMB-IGERT fellowship to RH; Cancer center at Illinois seed grant and Prairie Dragon Paddlers and?NSF EAGER awards and NIH (GM132458 and AG065748)?to KVP; and NSF (1243372 and 1818286) and NIH (GM125196) awards to SGP. The authors declare no competing financial interests.",
year = "2020",
month = nov,
doi = "10.1080/15384101.2020.1829823",
language = "English (US)",
volume = "19",
pages = "2927--2938",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Taylor and Francis Ltd.",
number = "21",
}