Bod1l is required to suppress deleterious resection of stressed replication forks

Recognition, repair and restart of damaged replication forks are essential for maintaining genome stability, and are coordinated by the combined action of the Fanconi Anaemia and homologous recombination pathways. A vital function of these pathways is to protect stalled replication forks from uncontrolled nucleolytic activity, which may otherwise cause irreparable damage to the genome. Here we identify BOD1L as a component of a replication fork protection pathway that safeguards genome stability after replication stress. Loss of BOD1L in cells confers exquisite sensitivity to replication stress and uncontrolled resection of damaged replication forks due to a failure to stabilise Rad51 at sites of damage. Blocking DNA2-dependent resection or down regulation of the BLM and Fbh1 helicases suppresses catastrophic fork processing and the accumulation of gross chromosomal damage in BOD1L deficient cells. Thus, our work implicates BOD1L as a critical regulator of genomic integrity that restrains nucleolytic degradation of damaged replication forks.