Evidence map›Paper›PMID 34534348›Full record

ArticleNucleic acids research2021

The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase.

Kimberlie A Wittig, Courtney G Sansam, Tyler D Noble, Duane Goins, Christopher L Sansam

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 17 citations in OpenAlex.

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  12. DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kimberlie A WittigDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.ORCID 0000-0002-8993-4007
Courtney G SansamCell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.ORCID 0000-0002-0253-8643
Tyler D NobleDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.ORCID 0000-0002-6073-7691
Duane GoinsCell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.ORCID 0000-0003-3154-9007
Christopher L SansamDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.ORCID 0000-0002-0545-2693
Oklahoma Medical Research Foundation · US

Funding

Mechanisms Regulating DNA Replication in the Developing Vertebrate EmbryoR01GM121703 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI SANSAM, CHRISTOPHER L · 2017 to 2021
$1.9M
NIGMS NIH HHS R01 GM121703
6 · The paper itself

Abstract

A DNA replication program, which ensures that the genome is accurately and wholly replicated, is established during G1, before the onset of S phase. In G1, replication origins are licensed, and upon S phase entry, a subset of these will form active replisomes. Tight regulation of the number of active replisomes is crucial to prevent replication stress-induced DNA damage. TICRR/TRESLIN is essential for DNA replication initiation, and the level of TICRR and its phosphorylation determine the number of origins that initiate during S phase. However, the mechanisms regulating TICRR protein levels are unknown. Therefore, we set out to define the TICRR/TRESLIN protein dynamics throughout the cell cycle. Here, we show that TICRR levels are high during G1 and dramatically decrease as cells enter S phase and begin DNA replication. We show that degradation of TICRR occurs specifically during S phase and depends on ubiquitin ligases and proteasomal degradation. Using two targeted siRNA screens, we identify CRL4DTL as a cullin complex necessary for TICRR degradation. We propose that this mechanism moderates the level of TICRR protein available for replication initiation, ensuring the proper number of active origins as cells progress through S phase.

Indexed as

S PhaseCarrier ProteinsCDC2 Protein KinaseCell CycleCell Cycle ProteinsCell Line, TumorCullin ProteinsCyclin-Dependent Kinase 2DNA-Binding ProteinsHumansProliferating Cell Nuclear AntigenReceptors, Interleukin-17Ubiquitin-Protein LigasesCarrier ProteinsCDC2 Protein KinaseCDC45 protein, humanCDK1 protein, humanCDK2 protein, humanCell Cycle ProteinsCullin ProteinsCyclin-Dependent Kinase 2DDB1 protein, humanDNA-Binding ProteinsIL17RB protein, humanMTBP protein, humanProliferating Cell Nuclear AntigenReceptors, Interleukin-17TICRR protein, humanUbiquitin-Protein Ligases

Identifiers

PMID34534348
PMCPMC8501952
OpenAlexW3199954500

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.