Structural highlights
Function
PCNA_HUMAN Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.[1] [2]
Publication Abstract from PubMed
F-box DNA helicase 1 (FBH1) is involved in the regulation of cell responses to replicative stress. FBH1 is recruited to stalled DNA replication fork by PCNA where it inhibits homologous recombination and catalyzes fork regression. Here, we report the structural basis for the molecular recognition of two distinctly different motifs of FBH1, FBH1(PIP) and FBH1(APIM), by PCNA. The crystal structure of PCNA in complex with FBH1(PIP) and analysis of NMR perturbations reveal overlapped FBH1(PIP) and FBH1(APIM) binding sites of PCNA and the dominant contribution of FBH1(PIP) in this interaction.
Molecular insight into the PCNA-binding mode of FBH1.,Liu J, Chaves-Arquero B, Wei P, Tencer AH, Ruiz-Albor A, Zhang G, Blanco FJ, Kutateladze TG Structure. 2023 May 4;31(5):511-517.e3. doi: 10.1016/j.str.2023.03.004. Epub 2023 , Mar 28. PMID:36990095[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Burkovics P, Hajdu I, Szukacsov V, Unk I, Haracska L. Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage. Nucleic Acids Res. 2009 Jul;37(13):4247-55. doi: 10.1093/nar/gkp357. Epub 2009, May 13. PMID:19443450 doi:10.1093/nar/gkp357
- ↑ Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105
- ↑ Liu J, Chaves-Arquero B, Wei P, Tencer AH, Ruiz-Albor A, Zhang G, Blanco FJ, Kutateladze TG. Molecular insight into the PCNA-binding mode of FBH1. Structure. 2023 May 4;31(5):511-517.e3. PMID:36990095 doi:10.1016/j.str.2023.03.004
