DNA replication stress as a hallmark of cancer.

By Morgane Macheret, T. Halazonetis. Annual Review of Pathology, 2015

751 citations recorded by the source corpus.

Human cancers share properties referred to as hallmarks, among which sustained proliferation, escape from apoptosis, and genomic instability are the most pervasive. The sustained proliferation hallmark can be explained by mutations in oncogenes and tumor suppressors that regulate cell growth, whereas the escape from apoptosis hallmark can be explained by mutations in the TP53, ATM, or MDM2 genes. A model to explain the presence of the three hallmarks listed above, as well as the patterns of genomic instability observed in human cancers, proposes that the genes driving cell proliferation induce DNA replication stress, which, in turn, generates genomic instability and selects for escape from apoptosis. Here, we review the data that support this model, as well as the mechanisms by which oncogenes induce replication stress. Further, we argue that DNA replication stress should be considered as a hallmark of cancer because it likely drives cancer development and is very prevalent.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/7b581961d5044ef6bae13e65c0b17bdc42c55502

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. Stephen P. Jackson
2. Y. Fouad
3. C. Aanei

In Molecular Biology

1. Andrew N. Blackford
2. John N. Weinstein
3. T. Soussi
4. Stephen P. Jackson
5. Olivier Lichtarge
6. Y. Fouad
7. C. Aanei
8. Yosef Shiloh

In Oncology

1. Andrew N. Blackford
2. John N. Weinstein
3. T. Soussi
4. Stephen P. Jackson
5. Olivier Lichtarge
6. Y. Fouad
7. C. Aanei
8. Yosef Shiloh

Citations in the corpus

• DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in C. elegans (2023, neutral): “Initiation is frequently mis-regulated in human cancer and represents an interesting target for new anti-cancer therapeutics (3, 4).”
• Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas (2018, neutral): “For example, HR defects are common in many cancer types and may compromise successful DNA replication and genome stability (Macheret and Halazonetis, 2015; Zeman and Cimprich, 2014).”
• Revisiting the hallmarks of cancer. (2017, positive): “For genomic instability, we choose to view it as a stress (Hallmark B) allowed-and frequently utilized-by cancer cells where DNA damage response is altered [204, 205].”
• ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response. (2017, background): “In line with this, ATM is frequently mutated in human cancers (Macheret and Halazonetis, 2015).”
• Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas (2019, background): “…p53 tumor suppressor protein is a transcription factor that inhibits cell division or survival in response to various stresses, thus acting as a key failsafe mechanism of cellular anti-cancer defenses (Kastenhuber and Lowe, 2017; Vousden and Prives, 2009; Macheret and Halazonetis, 2015).”