Radiotherapy is an important treatment option for many @entity1 @entity5 . Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various @entity5 . The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via @entity1603 ( @entity1603 ) nuclear foci detection at sites of single stranded DNA. yH2AX co-localised with these @entity1603 foci. @entity5345 and @entity24749 foci formed in T98G bystander cells. Using @entity15126 mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that @entity15126 but not ATM was required for the recruitment of @entity24749 to sites of replication associated DNA damage in bystander cells whereas @entity5345 bystander foci were ATM-dependent. Phospho- @entity23902 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the @entity23902 inhibitor @entity42840 but increased radioresistance of bystander cells. This study identifies @entity5345 , @entity24749 and @entity23902 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation.

@entity5345 , @entity24749 and XXXX are potential molecular targets for the modulation of a radiation-induced DNA damage response in bystander cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1603 :: ('MESH:D001973', 'Chemical') :: ['BrdU', 'bromodeoxyuridine'] @entity15126 :: ('545', 'Gene') :: ['ATR'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers'] @entity24749 :: ('2177', 'Gene') :: ['FANCD2'] @entity23902 :: ('1111', 'Gene') :: ['Chk1'] @entity42840 :: ('MESH:C054852', 'Chemical') :: ['UCN-01']
@entity23902 :: (1111,Gene) :: ['Chk1']
