Mammalian DNA damage repair pathways and checkpoints. Various exogenous and endogenous sources can generate damaged DNA. In response to DNA damage cells activate the appropriate DNA damage repair and checkpoint pathways or apoptosis. Lesions of single or double-stranded DNA lead to the activation of cell cycle checkpoints and a number of DNA damage repair pathways including MMR (mismatch repair), BER (base excision repair), NER (nucleotide excision repair), TLS (translesion DNA synthesis), HR (homologous recombination) and NHEJ (non-homologous end joining). Impaired repair of damaged DNA can lead to accumulation of, mutations and genomic instability. In addition, defective repair of damaged DNA can lead to aging as well as predisposition for various genetic diseases including cancer and immunodeficiency.