Table 1.

Brief description of DNA repair pathways in human cells. See text for details on repair by NR and NHEJ.

DNA repair pathways
mismatch repair (MMR)	DNA mismatches can arise during normal DNA replication and are repaired through MMR pathways involving the collective actions of a nuclease, polymerase and ligase [85]. Hereditary defects in MMR genes, such as occur in Lynch syndrome (also known as HNPCC, hereditary non-polyposis colorectal cancer) result in tumours with high levels of microsatellite instability
SSB repair	SSBs are recognized by PARP, which synthesizes PAR chains in the vicinity of the DNA break and promotes recruitment of DNA repair factors such as XRCC1 and LIG3 [86]. SSBs can occur as a result of IR or treatment with various chemical agents, and also arise as intermediates during BER and NER (see below)
base excision repair (BER)	involves the recognition, excision and replacement of damaged bases in cells, using enzymes that overlap with those required for SSB repair [87]
nucleotide excision repair (NER)	NER removes helix-distorting lesions from DNA, in particular the UV-induced photo lesions CPD (cyclobutane pyrimidine dimers) and 6-4PP (pyrimidine 6-4 pyrimidone photoproducts). Xeroderma pigmentosum (XP) is the archetypal human NER-deficiency syndrome, causing extreme sensitivity to UV light and very high incidences of skin malignancies. NER involves removal of a short oligonucleotide that includes the damaged lesion and subsequent restoration of the DNA sequence using the undamaged DNA as a template. Two sub-pathways of NER, global genome NER (GG-NER) and transcription coupled NER (TC-NER) use different mechanisms to recognize DNA lesions and promote either repair of DNA lesions throughout the genome or lesions encountered during active transcription, respectively [88]
trans-lesion synthesis (TLS)	TLS is a DNA damage bypass mechanism that protects against DSB break generation following replication fork stalling. It employs specialized DNA polymerases, principally from the Y-family, to replicate past the damaged DNA template and is inherently error-prone [89]
DNA interstrand cross-link (ICL) repair	ICLs can arise following exposure to a range of environmental mutagens, but are particularly abundant in cells following exposure to alkylating or platinum-based chemotherapeutics [90]. Fanconi anaemia is a rare genetic disorder causing aplastic anaemia, developmental defects and cancer predisposition, which is characterized by hypersensitivity to DNA interstrand cross-linking agents. It is caused by autosomal recessive mutations in one of 15 known genes that are required for ICL repair. The core Fanconi anaemia complex is made up of eight proteins (FANCA, B, C, E, F, G, L and M) required for the detection and repair of ICLs. ICLs can stall progression of the replication fork, causing replication fork collapse and the generation of a DNA DSB requiring coordination between translesion synthesis and homologous recombination mechanisms for repair [89]