Walking a tightrope: the complex balancing act of R-loops in genome stability

JR Brickner, JL Garzon, KA Cimprich - Molecular cell, 2022 - cell.com
Although transcription is an essential cellular process, it is paradoxically also a well-
recognized cause of genomic instability. R-loops, non-B DNA structures formed when …

DNA damage kinase signaling: checkpoint and repair at 30 years

MC Lanz, D Dibitetto, MB Smolka - The EMBO journal, 2019 - embopress.org
From bacteria to mammalian cells, damaged DNA is sensed and targeted by DNA repair
pathways. In eukaryotes, kinases play a central role in coordinating the DNA damage …

Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites

A Promonet, I Padioleau, Y Liu, L Sanz… - Nature …, 2020 - nature.com
R-loops have both positive and negative impacts on chromosome functions. To identify toxic
R-loops in the human genome, here, we map RNA: DNA hybrids, replication stress markers …

Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability

L Prendergast, UL McClurg, R Hristova… - Nature …, 2020 - nature.com
Collisions between the DNA replication machinery and co-transcriptional R-loops can
impede DNA synthesis and are a major source of genomic instability in cancer cells. How …

PCNA loaders and unloaders—One ring that rules them all

M Arbel, K Choudhary, O Tfilin, M Kupiec - Genes, 2021 - mdpi.com
During each cell duplication, the entirety of the genomic DNA in every cell must be
accurately and quickly copied. Given the short time available for the chore, the requirement …

Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions

KU Reusswig, J Bittmann, M Peritore, M Courtes… - Nature …, 2022 - nature.com
DNA replicates once per cell cycle. Interfering with the regulation of DNA replication
initiation generates genome instability through over-replication and has been linked to early …

Looping out of control: R-loops in transcription-replication conflict

C Kumar, D Remus - Chromosoma, 2024 - Springer
Transcription-replication conflict is a major cause of replication stress that arises when
replication forks collide with the transcription machinery. Replication fork stalling at sites of …

Mec1 is activated at the onset of normal S phase by low-dNTP pools impeding DNA replication

R Forey, A Poveda, S Sharma, A Barthe, I Padioleau… - Molecular cell, 2020 - cell.com
Summary The Mec1 and Rad53 kinases play a central role during acute replication stress in
budding yeast. They are also essential for viability in normal growth conditions, but the …

Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation

AW McClure, JFX Diffley - Elife, 2021 - elifesciences.org
The Rad53 DNA checkpoint protein kinase plays multiple roles in the budding yeast cell
response to DNA replication stress. Key amongst these is its enigmatic role in safeguarding …

Spatial organization and functions of Chk1 activation by TopBP1 biomolecular condensates

T Egger, L Morano, MP Blanchard, J Basbous… - Cell Reports, 2024 - cell.com
Assembly of TopBP1 biomolecular condensates triggers activation of the ataxia
telangiectasia-mutated and Rad3-related (ATR)/Chk1 signaling pathway, which coordinates …