For example, Brca1 associates with the hRad50-hMre11-p95/nibrin complex (nibrin is the gene mutated in Nigmegen breakage syndrome) in response to irradiation [ 32].
In accordance with these data, we observed phosphorylation of NBS1 (Nijmegen breakage syndrome 1) in response to bendamustine treatment in CLL cells, consistent with double-stranded DNA damage.
Lymphocytes showed no increase in chromosome breakage compared to control in response to mitomycin C challenge, excluding Fanconi anaemia.
In previous studies, a positive correlation between the levels of DNA strand breakage and HSP70 expression in response to decompression stress were also found by Pruski and Dixon [ 35].
Children in the family showed congenital developmental abnormalities and, lymphocytes from patient showed increased sensitivity to MMC, elevated chromosome breakage and pronounced G2 arrest in response to ICL damage, which are hallmarks of FA cells.
It is not impossible that some instances of delayed cytokinesis might be explained by checkpoint activation in response to the breakage of PICH-positive threads.
In response to double-strand breakage, stalled replication forks or DNA adducts, ATR complexed with ATR-interacting protein (ATRIP) is recruited and then phosphorylates a number of proteins involved in DNA damage, including H2AX, 53BP, TP53, NBS1 and CHEK1 [ 35- 38], thereby activating cell checkpoints, DNA repair or apoptosis.
The spectrin network is dynamic, accommodating reversible breakage and reformation of the dimer-dimer bonds in response to even moderate shear stress (e.g., Salomao et al., 2006).
CHEK2 (cell cycle checkpoint kinase 2, OMIM #604373) is a G2 checkpoint serine/threonine kinase that acts as a tumor suppressor in the nucleus in response to DNA double-strand breakage [ 1].
