Table 1 Summary of the human genetic disorders associated with DNA repair defects in the hematopoietic system

Gene	Function	Hematological phenotype in mice model	Disorders (hematologicalphenotype) in human
Key kinases
ATM	Plays a central role in DDR	BMF with HSCs depletion	Ataxia-telangiectasia (defective B cell differentiation, decreased circulating T cells)
ATR	Plays a central role in DDR	Accelerated aging, dwarfism, pancytopenia accumulation of fat in the BM	Seckel syndrome (pancytopenia)
Genes in the FA/BRCA pathway
FANCA, FANCB, FANCC, FANCE, FANCF, FANCG/XRCC9, FANCL, FANCT/UBE2T	Constituting FA core complex to promote FANCD2/I ubiquitination	Do not spontaneously develop a BMF phenotype, unless there is additional exogenous stress	FA (BMF)
FANCD2, FANCI	Recruitment of downstream nucleases to excise DNA-ICLs
FANCP/SLX4, FANCQ/ERCC4/XPF	Structure-specific exonucleases
FANCD1/BRCA2, FANCJ/BRIP1, FANCN/PALB2, FANCU/XRCC2, FANCW/RFWD3	Repair of DSB by promoting HR
FANCV/REV7/MAD2L2	Bypasss the crosslink remnants; and repair of DSB by promoting NHEJ
Genes in DSB repair machinery
DNA-PKcs/PRKDC	Serine/threonine-protein kinase that recruit interacts with LIG4-XRCC4 complex to promote DSB end ligation, and essential for V(D)J recombination	BMF with HSCs depletion	Severe combined immunodeficiency (decreased circulating T and B cells)
LIG4	ATP-dependent DNA ligase that interacts with XRCC4 to promote DSB end ligation, and essential for V(D)J recombination	Immunodeficiency, BMF with HSCs depletion	LIG4 syndrome (pancytopenia)
NBS1	A member of MRN complex, promotes DSB end resection	BMF with HSCs depletion	Nijmegen breakage syndrome (autoimmune hemolytic anemia,thrombocytopenia post hemolytic anemia, decreased circulating T and B cells)
Genes in MMR pathway
MLH1, MSH2, MSH6, PMS2	Repair of mismatches	Hematopoietic malignancies (leukemia and lymphoma	Mismatch repair cancer syndrome (leukemia)
Others
ERCC6L2	May play a role in the NER pathway	None	BMF syndrome
ADH5 and ALDH2 (Digenic)	Detoxifying enzymes that metabolize formaldehyde and acetaldehyde, respectively	Depletion of LT-HSCs and CLPs	AMED syndrome (BMF)

BM, bone marrow; BMF, bone marrow failure; CLPs, lymphoid progenitor; DDR, DNA damage response; DNA-ICLs, DNA inter-strand crosslinks; DSB, double-strand break; FA, Fanconi anemia; LT-HSCs, long-term hematopoietic stem cells; MMR, mismatch repair; MRN, MRE11-RAD50-NBS1; NER, nucleotide excision repair; NHEJ, non-homologous end joining; HR, homologous recombination; REF, reference