Perspectives on the role of bystander effect and genomic instability on therapy-induced secondary malignancy

AbstractCellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

Download Full-text

The role of telomere dysfunction in driving genomic instability

International Congress Series ◽

10.1016/j.ics.2006.10.013 ◽

2007 ◽

Vol 1299 ◽

pp. 146-149

Author(s):

Susan M. Bailey ◽

Eli S. Williams ◽

Robert L. Ullrich

Keyword(s):

Genomic Instability ◽

Telomere Dysfunction

Download Full-text

Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo

Carcinogenesis ◽

10.1093/carcin/bgm053 ◽

2007 ◽

Vol 28 (8) ◽

pp. 1831-1838 ◽

Cited By ~ 124

Author(s):

Igor Koturbash ◽

Alex Boyko ◽

Rocio Rodriguez-Juarez ◽

Robert J. McDonald ◽

Volodymyr P. Tryndyak ◽

...

Keyword(s):

Bystander Effect

Download Full-text

Protective role of humic acids against picloram-induced genomic instability and DNA methylation in Phaseolus vulgaris

Environmental Science and Pollution Research ◽

10.1007/s11356-017-9936-y ◽

2017 ◽

Vol 24 (29) ◽

pp. 22948-22953 ◽

Cited By ~ 6

Author(s):

Mahmut Sinan Taspinar ◽

Murat Aydin ◽

Burcu Sigmaz ◽

Nalan Yildirim ◽

Guleray Agar

Keyword(s):

Dna Methylation ◽

Phaseolus Vulgaris ◽

Genomic Instability ◽

Humic Acids ◽

Protective Role

Download Full-text

Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

eLife ◽

10.7554/elife.18020 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 16

Author(s):

Sabrina F Mansilla ◽

Agustina P Bertolin ◽

Valérie Bergoglio ◽

Marie-Jeanne Pillaire ◽

Marina A González Besteiro ◽

...

Keyword(s):

Genomic Instability ◽

Genomic Stability ◽

S Phase ◽

Fragile Sites ◽

Dna Lesions ◽

Cdk Inhibitor ◽

Cyclin Dependent Kinase ◽

Independent Manner ◽

Genomic Regions

The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21’s PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis.

Download Full-text