ETAA1 ensures proper chromosome segregation: A matter of S phase or mitosis?

Besteiro, Marina A. González; Gottifredi, Vanesa

doi:10.1083/jcb.201910157

Cited by 3 publications

(1 citation statement)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Micronuclei and anaphase aberrations are mechanistically related (17,(47)(48)(49), and this is supported by our data, as we observed a tight correlation between these two variables. Checkpoint defects precipitate chromosome mis-segregation as the result of S phase deregulation or spindle assembly checkpoint failure (50). In Chk1-depleted cells, the fact that UR-DNA precedes chromosome mis-segregation favors S phase deregulation.…”

Section: Chk1 Loss Leads To Cinmentioning

confidence: 99%

Mus81-Eme1–dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity

2020

Self Cite

View full text Add to dashboard Cite

Chromosome instability (CIN) underpins cancer evolution and is associated with drug resistance and poor prognosis. Understanding the mechanistic basis of CIN is thus a priority. The structure-specific endonuclease Mus81-Eme1 is known to prevent CIN. Intriguingly, however, here we show that the aberrant processing of late replication intermediates by Mus81-Eme1 is a source of CIN. Upon depletion of checkpoint kinase 1 (Chk1), Mus81-Eme1 cleaves under-replicated DNA engaged in mitotic DNA synthesis, leading to chromosome segregation defects. Supplementing cells with nucleosides allows the completion of mitotic DNA synthesis, restraining Mus81-Eme1–dependent DNA damage in mitosis and the ensuing CIN. We found no correlation between CIN arising from nucleotide shortage in mitosis and cell death, which were selectively linked to DNA damage load in mitosis and S phase, respectively. Our findings imply the possibility of optimizing Chk1-directed therapies by inducing cell death while curtailing CIN, a common side effect of chemotherapy.

show abstract

Section: Chk1 Loss Leads To Cinmentioning

confidence: 99%

Mus81-Eme1–dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity

2020

Self Cite

View full text Add to dashboard Cite

show abstract

p130RB2 positively contributes to ATR activation in response to replication stress via the RPA32-ETAA1 axis

Uchida

Niida

Sakai

et al. 2023

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer

Joo,

Ramirez,

Kabeche

2024

Cancers

View full text Add to dashboard Cite

Ataxia Telangiectasia and Rad3-related protein (ATR) is an apical kinase of the DNA Damage Response (DDR) pathway responsible for detecting and resolving damaged DNA. Because cancer cells depend heavily on the DNA damage checkpoint for their unchecked proliferation and propagation, ATR has gained enormous popularity as a cancer therapy target in recent decades. Yet, ATR inhibitors have not been the silver bullets as anticipated, with clinical trials demonstrating toxicity and mixed efficacy. To investigate whether the toxicity and mixed efficacy of ATR inhibitors arise from their off-target effects related to ATR’s multiple roles within and outside the DDR pathway, we have analyzed recently published studies on ATR’s non-canonical roles. Recent studies have elucidated that ATR plays a wide role throughout the cell cycle that is separate from its function in the DDR. This includes maintaining nuclear membrane integrity, detecting mechanical forces, and promoting faithful chromosome segregation during mitosis. In this review, we summarize the canonical, DDR-related roles of ATR and also focus on the non-canonical, multifaceted roles of ATR throughout the cell cycle and their clinical relevance. Through this summary, we also address the need for re-assessing clinical strategies targeting ATR as a cancer therapy based on these newly discovered roles for ATR.

show abstract

ETAA1 ensures proper chromosome segregation: A matter of S phase or mitosis?

Cited by 3 publications

References 11 publications

Mus81-Eme1–dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity

Mus81-Eme1–dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity

p130RB2 positively contributes to ATR activation in response to replication stress via the RPA32-ETAA1 axis

A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer

Contact Info

Product

Resources

About