This is in agreement with our previous results showing that down-regulation of DNA-PKcs or Ligase IV by RNAi increased fragile site instability only under replication stress [15].
In vitro hypoxia exposure can also mediate larger scale genomic instability by increasing fragile site induction, gene amplification and cellular DNA content [ 7- 9].
This sex difference may indicate that increased fragile sites expression (genomic instability) is the results of enhanced OS associated with SCZ.
With ever increasing fragile situations in the world, there is a push to identify effective tactics and responses to address the needs of the young in a crisis.
It is widely accepted that formula increases a fragile infant's risk of necrotizing enterocolitis -- the disease that claimed Micah's life.
As Stn1 knockdown also resulted in an increase in chromosomal aberrations, such as an increase in fragile sites detected on metaphase chromosomes, it is likely that these nontelomeric DDR foci were a result of chromosome breakage at nontelomeric loci (Fig. S4B, Supporting information).
Failure to restart telomeric replication forks, due to Ctc1 loss, has been shown to lead to an increase in fragile telomeres, stochastic and accelerated telomere attrition, an increase in single-strand G-rich telomeric DNA, and a dramatically shortened replicative potential (Gu et al., 2012).
Knockdown of hStn1 in a 21% oxygen atmosphere (Fig. S2A, Supporting information), or addition of aphidicolin, did not further increase the fragile telomere phenotype of human fibroblasts (Fig. S2B, Supporting information), supporting the model that Stn1 functions in the same pathway as polymerase α to facilitate replication of telomeres damaged by oxidative stress.
Furthermore, the drug aphidicolin, an inhibitor of polymerase α which by itself causes an increase in fragile telomeres (Sfeir et al., 2009), did not additionally increase the fragile and aberrant telomere phenotype of hStn1 knockdown cultures.
