DDR defects in hematologic malignancies. The core FA complex and its downstream effectors are involved in the recognition and resolution of interstrand crosslinks (ICLs). ATM phosphorylates Chk1 and p53 as a prerequisite for induction of apoptosis in the presence of DNA damage. NBN regulates ATM–dependent DNA damage signaling and DNA DSB end resection, whereas BLM mediates replication fork stability. SAMHD1 participates in the processing of stalled replication forks that require HRR for their resolution. The spliceosome component SF3B1 regulates the level of BRCA1, a scaffold protein that facilitates the assembly of HRR effectors, whereas the cohesin complex (STAG2, RAD21, SMC1, and SMC3) regulates HRR by holding sister chromatids in proximity to facilitate strand invasion. MSH2, MSH6, PMS2, and MLH1 are components of MMR. RNase H2 has a role in RER involving the resolution of ribonucleotides erroneously embedded during DNA replication. Proteins acting upstream of HRR are presented in colored boxes if altered in hematologic malignancies, or white boxes if not.