With the application of engineered nucleases, DSBs
are induced at selected target sites and then trigger various DNA repair processes, via the homology-directed repair (HDR) (termed HR previously), the nonhomologous end joining (NHEJ), or the recently identified microhomology-mediated end joining (MMEJ) pathways [10, 11].
HPV integration is facilitated by the DNA damage or DSBs
induced by oxidative stress or disruption of viral E2 ORF, which results in the inactivation of E2 protein that negatively regulates the expression of E6 and E7 viral oncogenes .
For example, the FANCM protein detects the stalled replication fork caused by interstrand crosslinks (ICLs); the MRN complex is the typical sensor of DSBs
during S/G2 phase; the Ku70/Ku80 heterodimer is the primary DSBs
sensor during G1, while replication protein A (RPA) overcoats single-strand DNA (ssDNA) found either at processed DSB
overhangs to be repaired by HR or at stalled replication forks .
We next exposed L-02 cells to [H.sub.2][O.sub.2], which induces oxidative stress and generates DSBs
, and further evaluated the antioxidant effects induced by a low concentration of CaA.
Although [H.sub.2][O.sub.2] induces primarily SSBs that are randomly distributed within DNA, bleomycin produces SSBs, DSBs
, and clustered DNA damage (Regulus et al.
With the development of artificial site-specific nucleases, including zinc finger nucleases (ZFNs) [4, 5], transcription activator-like effector nucleases (TALENs) [6-10], and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system [11, 12], the rate of homologous recombination is significantly elevated by producing a double-stranded break (DSB
) at the desired site.
Such findings take on added significance in view of the fact that the efficacy of DNA DSB
repair mechanisms become attenuated in aged oocytes.
So, at the same time the presence of BPV is causing DSBs
, the virus affects the repair system, favoring oncogenic process associated with unrepaired DSBs
BACKGROUND: It is widely accepted that DNA double-strand breaks (DSBs
) and their misrepair in stem cells are critical events in the multistage origination of various leukemias and tumors, including gliomas.
FVS spokeswoman Ilze Meistere told LETA that the SIA DSBS
and SIA J Investment have been shut down for hygiene violations.