Evidence map›Paper›PMID 41446221›Full record

ArticlebioRxiv : the preprint server for biology2025

A new model for coordinating the functions of TIMELESS at the replication fork.

Sameera Vipat, Rohan Harolikar, Karina Šapovalovaitė, Naga Raviteja Chavata, Syed Shahid Musvi, Arthur Morgunov, Sigvard Vällo, Tatiana N Moiseeva

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Sameera VipatDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.
Rohan HarolikarDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, 15213, Pittsburgh, PA.
Karina ŠapovalovaitėDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.
Naga Raviteja ChavataDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.
Syed Shahid MusviDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.
Arthur MorgunovDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.
Sigvard VälloDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.
Tatiana N MoiseevaDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, 12618, ESTONIA.

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
NCI NIH HHS P30 CA047904
6 · The paper itself

Abstract

TIMELESS is an essential protein that supports a multitude of various cell functions, from replication fork progression through intrinsic barriers in the genome and DNA damage checkpoint to double strand break repair, transcription, and circadian rhythm. How TIMELESS coordinates its various roles at the replication fork and in DNA damage response, and how its canonical position at the leading edge of the replication fork could facilitate its role in DNA damage checkpoint, remain poorly understood. Using an auxin-inducible degron system, we show that TIMELESS-depleted cells exhibited S phase entry defects, and compromised chromatin loading of CLASPIN and TIPIN - the other two components of the Fork Protection Complex (FPC). We further show that FPC chromatin loading was concurrent with the activation of the replicative helicase, but also required proficient DNA synthesis. Proximity labelling experiments suggested the existence of more than one molecule of TIMELESS per replication fork. TIMELESS interaction with the replicative helicase was essential for the speed of replication fork progression, but not for the role of TIMELESS in the activation of the replication checkpoint. Our data propose a new model for coordinating essential functions of TIMELESS in replication fork progression and checkpoint activation.

Identifiers

PMID41446221
PMCPMC12724444

What OpenQuestion holds

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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.