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Article
| Open Access
Genotoxic stress and viral infection induce transient expression of APOBEC3A and pro-inflammatory genes through two distinct pathways
The cytidine deaminase APOBEC3A is a main source of mutagenesis in many types of cancer. Here the authors reveal that transient up-regulation of APOBEC3A and other pro-inflammatory genes can occur due to viral infection and genotoxic stress via multiple pathways.
- Sunwoo Oh
- , Elodie Bournique
- & Rémi Buisson
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Article
| Open Access
Dpb4 promotes resection of DNA double-strand breaks and checkpoint activation by acting in two different protein complexes
The histone folding protein Dpb4 forms histone-like dimers within the ISW2 complex and the Pol ε complex in S. cerevisiae. Here the authors reveal insights into two distinct functions that Dpb4 exerts at DSBs depending on its interactors.
- Erika Casari
- , Elisa Gobbini
- & Maria Pia Longhese
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Article
| Open Access
SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks
The fork protection complex (FPC), including the proteins TIMELESS and TIPIN, stabilizes the replisome to ensure unperturbed fork progression during DNA replication. Here the authors reveal that that SDE2, a PCNA-associated protein, plays an important role in maintaining active replication and protecting stalled forks by regulating the replication fork protection complex (FPC).
- Julie Rageul
- , Jennifer J. Park
- & Hyungjin Kim
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Article
| Open Access
BRD4 prevents the accumulation of R-loops and protects against transcription–replication collision events and DNA damage
In order to avoid transcription-replication conflicts (TRCs) on shared DNA templates, cell must maintain strict spatiotemporal co-ordination of transcription with replication. Here the authors uncover a role for BRD4 in preventing TRCs and DNA damage checkpoint signaling in oncogenic cells.
- Fred C. Lam
- , Yi Wen Kong
- & Michael B. Yaffe
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Article
| Open Access
Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner
Oncogene-induced replication stress (RS) promotes cancer development. Here, the authors report that cancer cells adapt to oncogene-induced RS by overexpressing downstream components of ATR-CHK1 pathway, Claspin and Timeless, which have protective role at the replication forks independent of their checkpoint function.
- Julien N. Bianco
- , Valérie Bergoglio
- & Philippe Pasero
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Article
| Open Access
Systems biology approach reveals a link between mTORC1 and G2/M DNA damage checkpoint recovery
DNA damage induces checkpoints to ensure that damage is not transferred to the next generation, but the molecular pathways responsible for checkpoint recovery are not clear. Here the authors show that the nutrient sensor mTORC1 is a determinant for G2/M checkpoint recovery through regulation of cyclin B1 and PLK1 expression.
- Hui-Ju Hsieh
- , Wei Zhang
- & Guang Peng
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Article
| Open Access
Persistent repair intermediates induce senescence
Cells with damaged DNA can permanently exit the cell cycle during the G2 phase or recover spontaneously entering mitosis. Here the authors reveal that the decision to exit from the cell cycle in G2 is dependent on the presence of repair intermediates associated with homologous recombination.
- F. M. Feringa
- , J. A. Raaijmakers
- & R. H. Medema
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Article
| Open Access
The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects
SWR-C and its substrate the histone variant Htz1 are considered important for genome maintenance. Here the authors reveal that SWR-C/Htz1 plays a critical role during replication stress caused by absence of the replication fork progression proteins Mrc1/Tof1/Csm3.
- Anjana Srivatsan
- , Bin-Zhong Li
- & Richard D. Kolodner
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Article
| Open Access
FAN1 interaction with ubiquitylated PCNA alleviates replication stress and preserves genomic integrity independently of BRCA2
FANCD2-associated nuclease 1 (FAN1) is a key protein involved in the metabolism of DNA and in human pathologies. Here, the authors show that FAN1 directly interacts with PCNA at stalled replication forks to control their progression and prevent their collapse.
- Antonio Porro
- , Matteo Berti
- & Josef Jiricny
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Article
| Open Access
Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
DNA replication stress drives genome instability and cancer. Here, Ölmezer and colleagues show that the helicase activity of multifunctional enzyme Dna2 suppresses dead-end replication structures that impair chromosome segregation if not removed by Holliday junction resolvase Yen1 in yeast.
- Gizem Ölmezer
- , Maryna Levikova
- & Ulrich Rass
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Article
| Open Access
The tumour suppressor CYLD regulates the p53 DNA damage response
CYLD is a deubiquitinase known to act as a tumour suppressor in different models of carcinogenesis. Here, the authors show that CYLD suppresses carcinogen-induced tumorigenesis by deubiquitinating p53 and promoting its stabilization and activation in response to DNA damage.
- Vanesa Fernández-Majada
- , Patrick-Simon Welz
- & Manolis Pasparakis
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Rad54B serves as a scaffold in the DNA damage response that limits checkpoint strength
Rad54B is a poorly characterized DNA damage repair protein homologous to Rad54, a protein implicated in DNA damage repair through homologous recombination. Here the authors implicate Rad54B as a modulator of the DNA damage response through its interaction with the MDM2–MDMX complex to regulate p53 degradation.
- Takaaki Yasuhara
- , Takahiko Suzuki
- & Kiyoshi Miyagawa
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Article
| Open Access
Base excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy
The chemotherapeutic drug 5-fluorouracil causes cell toxicity by inducing DNA lesions. Here, SenGupta et al. use C. elegansto show that components of the base excision repair and the mismatch repair pathways function together in the response to 5-fluorouracil, resulting in activation of the DNA damage checkpoint and induction of autophagy.
- Tanima SenGupta
- , Maria Lyngaas Torgersen
- & Hilde Nilsen
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p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression
Cellular senescence is characterized by the cessation of cell growth and the expression of the p16 protein. In this study, inhibition or loss of p300, a histone acetyltransferase, is shown to result in senescence that occurs independently of p16 and is associated with histone hypoacetylation and altered replication timing.
- Alexandre Prieur
- , Emilie Besnard
- & Jean-Marc Lemaitre
TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells