Part of: Cancer Cell Line Encyclopedia (CCLE) project.
Part of: COSMIC cell lines project.
Part of: ENCODE project common cell types; tier 3.
Characteristics: Radiosensitive (PubMed=7494872).
Characteristics: Has a near pentaploid phenotype.
Microsatellite instability: Stable (MSS) (Sanger).
Sequence variation: Heterozygous for PRKDC p.Thr1351Profs*8 (c.4051delA) (PubMed=11418067; CCLE).
Sequence variation: Homozygous for PTEN p.Pro204fs*17 (c.610delC) (ATCC; CCLE; Cosmic-CLP).
Sequence variation: Homozygous for TP53 p.Glu286lys (c.856G>A) (PubMed=11023613; CCLE; Cosmic-CLP).
Omics: Deep exome analysis.
Omics: Deep RNAseq analysis.
Omics: DNA methylation analysis.
Omics: SNP array analysis.
Omics: Transcriptome analysis.
Genome ancestry: African=1.01%; Native American=0%; East Asian, North=2.75%; East Asian, South=0%; South Asian=0%; European, North=67.68%; European, South=28.55% (PubMed=30894373).
Caution: Was incorrectly stated to have deleterious mutations in ATM in PubMed=12105990.
DT Created: 04-04-12; Last updated: 06-09-19; Version: 26
The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair. However, here we show that blocking chromatin assembly, via knockdown of the histone chaperones ASF1 or CAF-1 or a mutation that prevents ASF1A binding to histones, hinders Rad51 loading onto ssDNA during homologous recombination. This is a consequence of reduced recruitment of the Rad51 loader MMS22L-TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end resection, persistent activation of the ATR-Chk1 pathway, and cell cycle arrest. In agreement, histones occupy ssDNA during DNA repair in yeast. We also uncovered DNA-PKcs-dependent DNA damage-induced ASF1A phosphorylation, which enhances chromatin assembly, promoting MMS22L-TONSL recruitment and, hence, Rad51 loading. We propose that transient assembly of newly synthesized histones onto ssDNA serves to recruit MMS22L-TONSL to efficiently form the Rad51 nucleofilament for strand invasion, suggesting an active role of chromatin assembly in homologous recombination.
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