PMID:26089390

Citation	Keka, IS, Mohiuddin, , Maede, Y, Rahman, MM, Sakuma, T, Honma, M, Yamamoto, T, Takeda, S and Sasanuma, H (2015) Smarcal1 promotes double-strand-break repair by nonhomologous end-joining. Nucleic Acids Res. 43:6359-72
Abstract	Smarcal1 is a SWI/SNF-family protein with an ATPase domain involved in DNA-annealing activities and a binding site for the RPA single-strand-DNA-binding protein. Although the role played by Smarcal1 in the maintenance of replication forks has been established, it remains unknown whether Smarcal1 contributes to genomic DNA maintenance outside of the S phase. We disrupted the SMARCAL1 gene in both the chicken DT40 and the human TK6 B cell lines. The resulting SMARCAL1(-/-) clones exhibited sensitivity to chemotherapeutic topoisomerase 2 inhibitors, just as nonhomologous end-joining (NHEJ) null-deficient cells do. SMARCAL1(-/-) cells also exhibited an increase in radiosensitivity in the G1 phase. Moreover, the loss of Smarcal1 in NHEJ null-deficient cells does not further increase their radiosensitivity. These results demonstrate that Smarcal1 is required for efficient NHEJ-mediated DSB repair. Both inactivation of the ATPase domain and deletion of the RPA-binding site cause the same phenotype as does null-mutation of Smarcal1, suggesting that Smarcal1 enhances NHEJ, presumably by interacting with RPA at unwound single-strand sequences and then facilitating annealing at DSB ends. SMARCAL1(-/-)cells showed a poor accumulation of Ku70/DNA-PKcs and XRCC4 at DNA-damage sites. We propose that Smarcal1 maintains the duplex status of DSBs to ensure proper recruitment of NHEJ factors to DSB sites.
Links	PubMed PMC4513880 Online version:10.1093/nar/gkv621
Keywords	Animals; Camptothecin/toxicity; Cell Line; Chickens; DNA Breaks, Double-Stranded; DNA Damage; DNA End-Joining Repair; DNA Helicases/chemistry; DNA Helicases/genetics; DNA Helicases/physiology; DNA-Binding Proteins/metabolism; G1 Phase/genetics; Gene Deletion; Humans; Protein Structure, Tertiary
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SMAL1		GO:0006303: double-strand break repair via nonhomologous end joining	ECO:0000315:		P		Human cells with a deletion in Smarcal1 have less frequent double stranded break repair events. This is seen in Figure 5B where cells with the Smarcal1 deletion show a 4fold decrease in DSB repair events compared to wild type.	complete CACAO 12729

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