The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin.

Nature Communications
Sang-Min JangMirit I Aladjem

Abstract

Cell cycle progression in mammals is modulated by two ubiquitin ligase complexes, CRL4 and SCF, which facilitate degradation of chromatin substrates involved in the regulation of DNA replication. One member of the CRL4 complex, the WD-40 containing protein RepID (DCAF14/PHIP), selectively binds and activates a group of replication origins. Here we show that RepID recruits the CRL4 complex to chromatin prior to DNA synthesis, thus playing a crucial architectural role in the proper licensing of chromosomes for replication. In the absence of RepID, cells rely on the alternative ubiquitin ligase, SKP2-containing SCF, to progress through the cell cycle. RepID depletion markedly increases cellular sensitivity to SKP2 inhibitors, which triggered massive genome re-replication. Both RepID and SKP2 interact with distinct, non-overlapping groups of replication origins, suggesting that selective interactions of replication origins with specific CRL components execute the DNA replication program and maintain genomic stability by preventing re-initiation of DNA replication.

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Citations

Apr 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·David de SemirMohammed Kashani-Sabet
Oct 3, 2020·Experimental & Molecular Medicine·Sang-Min JangMirit I Aladjem
Sep 13, 2019·PLoS Genetics·Babatunde Ekundayo, Franziska Bleichert
Jun 7, 2019·Cold Spring Harbor Molecular Case Studies·Kirsten E CraddockWendy K Chung
Feb 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ukhyun JoYves Pommier
Jan 6, 2021·Nature Chemical Biology·Xinyan ChenChao Xu
Apr 16, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sang-Min JangMirit I Aladjem
Jun 10, 2021·Nature Communications·Haiqing FuMirit I Aladjem
Jun 3, 2021·Cancers·Jonathan J Morgan, Lisa J Crawford
Jun 26, 2021·Biochemical and Biophysical Research Communications·Dong-Kyu KimSang-Min Jang

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Datasets Mentioned

BETA
GSE114703

Methods Mentioned

BETA
ubiquitination
RepID
neddylation
pull-down
FACS
immunoprecipitation
flow cytometry
ChIP-Seq
PCR
transfection

Software Mentioned

FIJI
Genomatix
BedIntersect
Integrative Genomics Viewer ( IGV
ImageJ
SICER
FlowJo
BedSubtract

Related Concepts

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