Exploiting the homologous recombination DNA repair network for targeted cancer therapy

Table 1 An overview of DNA damage lesions and repair mechanisms in cancer suppression

DNA repair pathway	NER	BER	HR	NHEJ	MMR
DNA lesions	(6-4) PP	Uracil	Interstrand cross-link	Interstrand	A-G mismatch
	Bulky adduct	Abasic site	DSB	Cross-link	T-C mismatch
	CPD	8-oxoguanine		DSB	Insertion
	SSB	SSB			Deletion
Key molecules	XPA-XPG, RPA, ERCC1	DNA glycosylase, APE1, DNA poly β/δ/ε, XRCC1, DNA ligase 1/3	ATM, RAD50/MRE11/NBS1 RPA, BRCA1, BRCA2, RAD51	KU70-KU80, DNAPK, XRCC4	hMSH2/6 hMLH1, FEN1, Exonuclease 1
Cancer linkage	Xeroderma pigmentosum (skin cancer)	XRCC1 (lung cancer)	Ataxia telangiectasia (lymphomas), nijmegen breakage syndrom (lymphomas), BRCA1/BRCA2 (breast and ovarian cancers), werner syndrome (various cancers), bloom syndrome (leukaemia, lymphoma, others), rothmund-thomson syndrome (osteosarcoma)	Ligase IV deficiency (leukemia)	HNPCC (colorectal cancer)

NER: Nucleotide-excision repair; BER: Base-excision repair; HR: Homologous recombination; NHEJ: Non-homologous end joining; DSB: Double strand break; MMR: Mismatch repair; (6-4) PP: Pyrimidine (6-4) pyrimidone; CPD: Cyclobutane pyrimidine dimers; HNPCC: Herditary non-ployposis colorectal cancer; SSB: Single strand break; RPA: DNA replication protein A; ERCC1: Excision repair cross-complementation group 1; RAD51: DNA repair protein RAD51 homolog 1; MRE11: Meiotic recombination 11 homolog 1; NBS1: Nijmegen B breakage syndrome 1; BRCA: Breast cancer susceptibility protein; DNAPK: DNA-dependent protein kinase catalytic subunit.