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Table 2 Identified key genes in synthetic lethality preclinical studies

From: Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation

Gene Chromosome Cellular process and mechanism In vitro In vivo Cancer type Reference
ARID1A 1p36.11 Target SWI/SNF complexes, which regulate chromatin remodeling. SWI/SNF complexes are involved in controlling the cell cycle, DNA replication, and repairing DNA damage. H1299, H2023, H2030 Smarca4-deficient genetically engineered mouse Lung cancer [34]
ATM 11q22.3 Activates cell cycle checkpoints; recognizes damaged DNA and triggers ATM-mediated DNA damage response pathway to repair damaged DNA strands. KC (850, 6059, 8878), AKC (995, 5615, 5980, 5982) AKC, KC, and SCID mouse Pancreatic cancer [35]
ATR 3q23 Cell cycle checkpoint signaling activation upon DNA stress and triggers ATR-mediated DNA damage sensing. Human-derived CLL and Mec1 cell line Primary CLL xenograft mouse Leukemia [36, 37]
BRCA1 17q21.31 Repair DNA double-strand breaks via ubiquitination, transcriptional regulation, and homologous recombination. A2780, HEK293, SUM149PT N/A Ovarian cancer [38]
BRCA2 13q13.1 Repair DNA double-strand breaks via ubiquitination, transcriptional regulation, and homologous recombination. PL2F7, Y3308Y BRCA-deficient mouse N/A [39]
CDC6 17q21.2 Initiation of DNA replication; regulates cell cycle. HCT-116, HKE-3 KRAS-induced lung cancer mouse Lung cancer [40, 41]
CDK1 10q21.2 Regulate cell cycle (G1/S and G2/M phase transitions). LIM1215, SW48 KRAS-mutated mouse N/A [42]
CDK2 12q13.2 Regulate cell cycle (G1/S phase transition). HACAT N/A N/A [43, 44]
CDK17 12q23.1 Serine-threonine protein kinase; regulate G2/M phase transition. HeLa, K562, MCF10A, MDA-MB-231, RPE1 N/A Breast cancer [45]
CHEK1 11q24.2 Serine-threonine protein kinase; triggers cell cycle arrest in response to DNA damage; integrate signals from ATR and ATM; phosphorylation of CDC25A to delay cell cycle progression following DNA double-strand breaks. PEO14, PEO23, SKOV3 SKOV3 xenograft mouse Ovarian cancer [46]
CHEK2 22q12.1 Serine-threonine protein kinase; triggers cell cycle arrest in response to DNA damage; integrate signals from ATR and ATM; phosphorylation of CDC25A to delay cell cycle progression following DNA double-strand breaks. Cal27, HN30, HN31, SCC61, UMSCC17A N/A Head and neck cancer [47]
GATA2 3q21.3 Zinc-finger transcription factor; regulate transcription genes. A549, H226, HL7702 A549 xenograft mouse Lung cancer [48]
KRAS 12p12.1 Transcriptional activator that regulates endothelial cells endothelin-1 gene expression. A549, H441 A549 xenograft mouse Lung cancer [49, 50]
MRE11 11q21 MRN complex component; DNA double-strand breaks repair via nonhomologous end-joining and homologous recombination activation in ATM-mediated checkpoint. V-C8 N/A N/A [51]
MYC 8q24.21 Regulate cell cycle progression, transcription, and apoptosis. Kelly, BE-2C, NLF, SK-N-AS, SHEP, MYCN-ER BALB/c nude mouse Neuroblastoma [52, 53]
NBN 8q21.3 MRN complex component; DNA double-strand breaks repair via nonhomologous end-joining and homologous recombination activation in ATM-mediated checkpoint. B220, Gr-1, Mac-1 Nbn-mutated mouse Leukemia [54]
PAK3 Xq23 Serine-threonine protein kinase; regulates cell cycle, cell migration, and apoptosis. CaSki, HeLa, HFK, SiHa N/A Cervical cancer [55]
PARP1 1q41.42 Regulate cell proliferation and differentiation; repair DNA single- and double-strand breaks. DLD-1, HEK293FT, KB1P-G3, KB2P, SUM149PT, U2OS BRCA2-mutated mouse Breast and ovarian cancer [56]
PLK1 16p12.2 Serine-threonine protein kinase; regulate cell proliferation and apoptosis; triggers G2/M transition. A549, H441, H522, T29 BALB/c and C57BL/6 nude mouse Lung cancer [57]
RAD50 5q31.1 MRN complex component; DNA double-strand breaks repair via nonhomologous end-joining and homologous recombination activation in ATM-mediated checkpoint. D1241, L1240, Q1262, WT N/A Metastatic small cell cancer [58]
RAD51 15q15.1 Repair DNA double-strand breaks via homologous recombination. HeLa, K562, M059, U2OS N/A N/A [59]
TP53 17p13.1 Major tumor suppressor; regulate cell cycle, senescence, and apoptosis. C4-2, LNCaP, U2OS NSG mouse Prostate cancer [60, 61]
53BP1 15q15.3 Repair DNA double-strand breaks by promoting non-homologous end-joining pathways while limiting homologous recombination. DOHH2, G452, HCC1187 OCI-LY (1, 8, 19), SUDHL-6, U2932, VAL NOD, NSG, and SCID mouse Lymphoma [62, 63]
WEE1 11p15.4 Serine-threonine protein kinase; regulates G2/M checkpoint via CDC2 inhibition. MCF7, MDA-MB-231, T-47D, Zr-75-1 Breast cancer xenograft NSG mouse Breast cancer [64]