Overview of DNA Repair in Trypanosoma cruzi, Trypanosoma brucei, and Leishmania major

Table 1

Gene	Function	Organism (Gene ID)	Experimental data	Ref.
BER Genes
Uracyl-DNA glycosylase; (UNG)	Excision of uracil in DNA	T. cruzi (Tc00.1047053511277.330)	(i) In vitro activity (enhanced by AP endonuclease)	[16, 17]
			(ii) Heterologous complementation of E. coli
AP endonuclease1	Cleavage of the phosphodiester bond at the 5^ side of AP site	T. cruzi (Tc00.1047053507083.30)	(i) Heterologous complementation of E. coli	[18]
		L. major (LmjF16.0680)	(i) Heterologous complementation of E. coli	[18–20]
			(ii) Increment of H2O2 and methotrexate resistance
POL𝛽	Polymerization of DNA; Strand displacement (long-patch); Cleavage of the 5^- dRP	T. cruzi (Tc00.1047053503955.20)	(i) In vitro activity; (ii) Kinetoplast localization	[21]
		T. brucei (Tb927.5.2780)		[22]
PARP	Binding to ssDNA; Stimulation of DNA synthesis and strand displacement	T. cruzi (Tc00.1047053509721.60)	(i) In vitro activity (enhanced by SSB)	[23]
NER Genes
TFIIH-TFB1	Component of TFIIH	T. brucei (Tb11.01.1200)	(i) Essential for initiating synthesis of spliced leader RNA
TFIIH-TFB2		T. brucei (Tb927.10.5210)
TFIIH-TFB4		T. brucei (Tb11.01.7730)		[24]
TFIIH-TFB5		T. brucei (Tb10.61.2600)
TFIIH-XPB	Component of TFIIH (helicase)	T. brucei (Tb11.01.7950Tb927.3.5100)	(i) Interaction with TSP1 and TSP2
TFIIH-XPD		T. brucei (Tb927.8.5980)	(i) Nuclear localization
TFIIH-TSP1	Trypanosomatid-specific component of TFIIH	T. brucei (Tb927.1.1080)	(i) Essential for initiating synthesis of spliced leader RNA	[24]
TFIIH-TSP2		T. brucei (Tb11.01.5700)	(i) Nuclear localization; (ii) Essential for initiating synthesis of spliced leader RNA
XAB2^∗	May function as a scaffold for protein complex formation	T. cruzi (Tc00.1047053509767.40)	(i) Putative	—
		T. brucei (Tb927.5.1340)	(i) Putative	—
		L. major (LmjF23.1550)	(i) Putative	—
MMR Genes
MSH2	Repair of single base-base and IDL mismatches; Heterodimers with MSH3 or MSH6	T. cruzi (Tc00.1047053507711.320)	(i) Three isoforms with different efficiencies	[25, 26]
			(ii) Involvement in oxidative stress response (independently from MLH1)
		T. brucei (Tb927.10.11020)	(i) Involvement in oxidative stress response (independently from MLH1)	[26–28]
			(ii) Microsatellite instability and MNNG tolerance in MSH2/MLH1 double mutants
			(iii) Regulatory role in HR
MLH1	Heterodimers with MutL homologs; Matchmaker for coordinating eventes from mismatch binding to DNA synthesis		(i) Microsatellite instability and MNNG tolerance in MSH2/MLH1 double mutants; (ii) Regulatory role in HR
		T. brucei (Tb927.8.6840)		[27, 28]
		NHEJ Genes
Ku70	DSB recognition	T. brucei (Tb927.3.5030)	(i) Telomere maintenance	[29, 30]
	DSB bridging nucleolytic processing of the ends
Ku80	Telomere maintenance	T. brucei (Tb927.6.1760)
HR Genes
Mre11	DSB end resection	T. brucei (Tb927.2.4390)	(i) Mre11 mutations cause impairment of HR and increased DNA damage sensitivity	[31, 32]
	Nuclease activities
Rad51	Recombinases		(i) Gene expression induced by DNA damaging agents; (ii) Involved in DSBs and oxidative lesions repair
		T. cruzi (Tc00.1047053503801.30)		[33]
		T. brucei (Tb11.01.0360)		(i) Null mutants led to impairments in VSG switch and DNA transformation, besides a higher sensitivity to genotoxic agents	[34]
		L. major (LmjF28.0550)	(i) Gene expression induced by DNA-damaging agents	[35]
		Dmc1	Recombinases	T. brucei (Tb09.211.1210)	(i) DMC1 mutation does not affect HR or VSG switching	[36]
BRCA2	ssDNA binding; Recombination mediator	T. brucei (Tb927.1.640)	(i) Expansion in the number of BRC repeats; (ii) BRCA2 mutants display antigenic variation impairment and genome instability	[37]
Rad51-3	ssDNA binding; Recombination mediator activity	T. brucei (Tb11.02.0150)	(i) Rad51-3 mutations resulted in reduced levels of VSG switching, altered RAD51 localization following DNA damage and DNA damage sensitized parasites	[38]
Rad51-5		T. brucei (Tzb10.389.1770)	(i) Rad51-5 mutations caused altered RAD51 localization following DNA damage and DNA damage sensitized parasites	[38]
TLS Genes
Pol𝜂	Error-free bypass of cis-syn cyclobutane pyrimidine dimers (CPDs)	T. cruzi (Tc00.1047053511911.120)	(i) Heterologous complementation of S. cerevisae; (ii) In vitro bypass of 8-oxoG; (iii) Overexpression increases H2O2 resistance	[39]
Pol𝜅	Bypass of N2-adducted dG lesions; Extension of mismatched primer termini	T. cruzi (Tc00.1047053503755.30)	(i) Mitochondrial localization; (ii) In vitro bypass of8-oxoG; (iii) DNA synthesis within recombination intermediates; (iv) Overexpression increases zeocin, gamma radiation, and H2O2 resistance	[40]