Molecular mechanisms of DNA replication control by mammalian RIF1 protein

Research output: Contribution to conferencePoster

Abstract

RIF1 was originally identified as a telomeric protein in budding yeast, but is now known to play diverse roles in chromosome stability throughout eukaryotes. RIF1 regulates initiation time of a subset of replication origins in fission yeast and mammalian cells.

Replication origin initiation requires activation of the MCM helicase through phosphorylation of MCM subunits by Dbf4-Dependent Kinase (DDK). We previously demonstrated that budding yeast Rif1 directs Protein Phosphatase 1 (PP1) to counteract phosphorylation of Mcm4, negatively regulating DNA replication in S. cerevisiae and ensuring cell cycle control over MCM complex activation.

PP1 interaction motifs are a conserved feature of RIF1 proteins, and human RIF1 has been reported to bind PP1. To test whether mammalian RIF1 regulates DNA replication by targeting PP1 activity, we have investigated the effects of mutating the PP1-interaction motifs in the human RIF1 protein. We find that PP1 interaction-defective RIF1 cannot substitute for wild-type RIF1 in controlling phosphorylation levels of human MCM complex proteins.

Our data support the idea that like yeast Rif1, the human RIF1 protein is a PP1 substrate-targeting subunit that regulates DNA replication by recruiting PP1 to counteract DDK-mediated phosphorylation. This replication regulatory mechanism therefore appears to be conserved from yeast to mammals.
Original languageEnglish
Publication statusPublished - Jul 2015
EventEMBO conference on DNA replication, chromosome segregation and cell division - England, Egham, United Kingdom
Duration: 27 Jul 201531 Jul 2015

Conference

ConferenceEMBO conference on DNA replication, chromosome segregation and cell division
CountryUnited Kingdom
CityEgham
Period27/07/1531/07/15

Fingerprint

Protein Phosphatase 1
DNA Replication
Proteins
Phosphorylation
Saccharomycetales
Replication Origin
Phosphotransferases
Minichromosome Maintenance Proteins
Yeasts
Chromosomal Instability
Schizosaccharomyces
Cell Cycle Checkpoints
Eukaryota
Saccharomyces cerevisiae
Mammals

Cite this

Hiraga, S-I. (2015). Molecular mechanisms of DNA replication control by mammalian RIF1 protein. Poster session presented at EMBO conference on DNA replication, chromosome segregation and cell division, Egham, United Kingdom.

Molecular mechanisms of DNA replication control by mammalian RIF1 protein. / Hiraga, Shin-Ichiro.

2015. Poster session presented at EMBO conference on DNA replication, chromosome segregation and cell division, Egham, United Kingdom.

Research output: Contribution to conferencePoster

Hiraga, S-I 2015, 'Molecular mechanisms of DNA replication control by mammalian RIF1 protein' EMBO conference on DNA replication, chromosome segregation and cell division, Egham, United Kingdom, 27/07/15 - 31/07/15, .
Hiraga S-I. Molecular mechanisms of DNA replication control by mammalian RIF1 protein. 2015. Poster session presented at EMBO conference on DNA replication, chromosome segregation and cell division, Egham, United Kingdom.
Hiraga, Shin-Ichiro. / Molecular mechanisms of DNA replication control by mammalian RIF1 protein. Poster session presented at EMBO conference on DNA replication, chromosome segregation and cell division, Egham, United Kingdom.
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