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Publication : Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen.

First Author  Jónsson ZO Year  1998
Journal  EMBO J Volume  17
Issue  8 Pages  2412-25
PubMed ID  9545252 Mgi Jnum  J:47375
Mgi Id  MGI:1203358 Doi  10.1093/emboj/17.8.2412
Citation  Jonsson ZO, et al. (1998) Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen. EMBO J 17(8):2412-25
abstractText  The DNA polymerase accessory factor proliferating cell nuclear antigen (PCNA) has been caught in interaction with an ever increasing number of proteins. To characterize the sites and functions of some of these interactions, we constructed four mutants of human PCNA and analysed them in a variety of assays. By targeting loops on the surface of the PCNA trimer and changing three or four residues at a time to alanine, we found that a region including part of the domain-connecting loop of PCNA and loops on one face of the trimer, close to the C-termini, is involved in binding to all of the following proteins: DNA polymerase delta, replication factor C, the flap endonuclease Fen1, the cyclin dependent kinase inhibitor p21 and DNA ligase I. An inhibition of DNA ligation caused by the interaction of PCNA with DNA ligase I was found, and we show that DNA ligase I and Fen1 can inhibit DNA synthesis by DNA polymerase delta/PCNA. We demonstrate that PCNA must be located below a considering the interacting region on PCNA for Fen1, this suggests an orientation for PCNA during DNA replication with the C-termini facing forwards, in the direction of DNA synthesis.
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