DNA repair in the context of chromatin: New molecular insights by the nanoscale detection of DNA repair complexes using transmission electron microscopy

DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair

“…Studies on the repair of DSBs after low-or high-LET irradiation revealed that rejoining of DSBs consists of a fast and a slow component and that DMSO reduces mainly the fast component of DSB-repair [5,[42][43][44], while slow repair is related to repair of complex DSBs, particularly by HRR [45,46]. The DMSO effect on the fast rejoining of DSBs thus suggests that NHEJ is particularly efficient in repairing lesions produced by the indirect effect.…”

Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: The molecular choreography

“…In conclusion, KAP1 Ser824 phosphorylation creates a C-terminal region that interferes with the interaction between CHD3's SUMO-interacting motif and the SUMO1 moiety of KAP1, thereby releasing CHD3 from heterochromatin at DSBs and enabling repair ( Bonner and coworkers identified phosphorylation of H2AX at Ser139 in the C-terminus (TQASQEY) in response to IR-induced DSBs as an immediate, sensitive indicator of IR exposure (reviewed in [155,[335][336][337]) and other DNA-damaging agents [338]. (In some systems such as the mouse brain, gH2AX (H2AX S139-P ) nuclear foci appear not to arise at all DSBs [339].) Per Gy of IR, $1% of the chromatin is modified, and a single DSB is associated with modification of several million bp of DNA [31,340].…”

“…The use of transmission electron microscopy combined with immunogold-labeling in cortical neurons has allowed the detection of phosphorylated Ku70 bound at IR-induced DNA breaks [339]. Pairs of gold beads separated by a distance of $15 nm are consistently seen, presumably reflecting two individual Ku70 molecules bound at the beak [339].…”

Telomere length and LINE1 methylation is associated with chromosomal aberrations in peripheral blood

“…Both global and localized changes in the chromatin structure are driven by DNA methylation and histone modifications, which directly affect the conformation of chromatin. While DNA lesions in euchromatin are detected and rejoined without any delay, DNA packaging in heterochromatin, which LINE1 elements are part of, appears to retard DNA strand break processing, leading to slower repair kinetics (Rü be et al, 2011). Hypothetically, more methylation of LINE1 results in less accessible chromatin that may slow down DNA repair and result in higher frequency of chromosomal aberrations (Baylin and Ohm, 2006).…”