Positive and negative control of DNA replication by human RIF1 protein

A safeguard mechanism

Research output: Contribution to conferencePoster

Abstract

We have previously shown that in budding yeast RIF1 protein negatively controls DNA replication by suppressing phosphorylation level of MCM protein, and that interaction with Protein Phosphatase 1 (PP1) is critical for this regulation.
Presence of PP1-interaction motifs is an evolutionarily conserved feature of RIF1 proteins, suggesting a fundamental importance of PP1 interaction for the function of RIF1 proteins. However, the importance of PP1 interaction in function of mammalian RIF1 proteins have not been addressed, despite the interaction with PP1 has been reported multiple times.
By combining an inducible mutant of human RIF1 protein and siRNA depletion of endogenous RIF1, we tested the importance of RIF1 protein and its PP1 interaction for controlling DNA replication. We found that PP1 interaction plays a critical role for RIF1 proteins to regulate DNA replication, by dephosphorylating MCM proteins.
We also discovered a novel role of RIF1 in promoting origin licensing during G1 phase. We will further discuss about possible role of RIF1 in securing the establishment of dormant origins.
Taken together, human RIF1 protein imposes both positive and negative regulations on DNA replication: ensuring proper origin licensing in G1 phase, as well as suppressing origin activations.
Original languageEnglish
Publication statusPublished - Nov 2016
Event10th 3R International Symposium - Matsue, Japan
Duration: 13 Nov 201617 Nov 2016
http://3r2016.com

Conference

Conference10th 3R International Symposium
CountryJapan
CityMatsue
Period13/11/1617/11/16
Internet address

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Staphylococcal Protein A
Protein Phosphatase 1
DNA Replication
Proteins
G1 Phase
Licensure
Saccharomycetales
Fungal Proteins
Small Interfering RNA
Phosphorylation

Cite this

Positive and negative control of DNA replication by human RIF1 protein : A safeguard mechanism. / Hiraga, Shin-ichiro; Garzon, Francisco Javier Hidalgo; Donaldson, Anne Dunlop.

2016. Poster session presented at 10th 3R International Symposium, Matsue, Japan.

Research output: Contribution to conferencePoster

Hiraga S, Garzon FJH, Donaldson AD. Positive and negative control of DNA replication by human RIF1 protein: A safeguard mechanism. 2016. Poster session presented at 10th 3R International Symposium, Matsue, Japan.
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N2 - We have previously shown that in budding yeast RIF1 protein negatively controls DNA replication by suppressing phosphorylation level of MCM protein, and that interaction with Protein Phosphatase 1 (PP1) is critical for this regulation. Presence of PP1-interaction motifs is an evolutionarily conserved feature of RIF1 proteins, suggesting a fundamental importance of PP1 interaction for the function of RIF1 proteins. However, the importance of PP1 interaction in function of mammalian RIF1 proteins have not been addressed, despite the interaction with PP1 has been reported multiple times. By combining an inducible mutant of human RIF1 protein and siRNA depletion of endogenous RIF1, we tested the importance of RIF1 protein and its PP1 interaction for controlling DNA replication. We found that PP1 interaction plays a critical role for RIF1 proteins to regulate DNA replication, by dephosphorylating MCM proteins. We also discovered a novel role of RIF1 in promoting origin licensing during G1 phase. We will further discuss about possible role of RIF1 in securing the establishment of dormant origins. Taken together, human RIF1 protein imposes both positive and negative regulations on DNA replication: ensuring proper origin licensing in G1 phase, as well as suppressing origin activations.

AB - We have previously shown that in budding yeast RIF1 protein negatively controls DNA replication by suppressing phosphorylation level of MCM protein, and that interaction with Protein Phosphatase 1 (PP1) is critical for this regulation. Presence of PP1-interaction motifs is an evolutionarily conserved feature of RIF1 proteins, suggesting a fundamental importance of PP1 interaction for the function of RIF1 proteins. However, the importance of PP1 interaction in function of mammalian RIF1 proteins have not been addressed, despite the interaction with PP1 has been reported multiple times. By combining an inducible mutant of human RIF1 protein and siRNA depletion of endogenous RIF1, we tested the importance of RIF1 protein and its PP1 interaction for controlling DNA replication. We found that PP1 interaction plays a critical role for RIF1 proteins to regulate DNA replication, by dephosphorylating MCM proteins. We also discovered a novel role of RIF1 in promoting origin licensing during G1 phase. We will further discuss about possible role of RIF1 in securing the establishment of dormant origins. Taken together, human RIF1 protein imposes both positive and negative regulations on DNA replication: ensuring proper origin licensing in G1 phase, as well as suppressing origin activations.

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