title: A BRCA1-interacting lncRNA regulates homologous recombination.
abstract: Long non-coding RNAs (lncRNAs) are important players in diverse biological processes. Upon DNA damage, cells activate a complex signaling cascade referred to as the DNA damage response (DDR). Using a microarray screen, we identify here a novel lncRNA, DDSR1 (DNA damage-sensitive RNA1), which is induced upon DNA damage. DDSR1 induction is triggered in an ATM-NF-κB pathway-dependent manner by several DNA double-strand break (DSB) agents. Loss of DDSR1 impairs cell proliferation and DDR signaling and reduces DNA repair capacity by homologous recombination (HR). The HR defect in the absence of DDSR1 is marked by aberrant accumulation of BRCA1 and RAP80 at DSB sites. In line with a role in regulating HR, DDSR1 interacts with BRCA1 and hnRNPUL1, an RNA-binding protein involved in DNA end resection. Our results suggest a role for the lncRNA DDSR1 in modulating DNA repair by HR.
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD, USA viveksharmabt@gmail.com mistelit@mail.nih.gov.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: Simran
authors.initials: S
authors.lastname: Khurana
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: Nard
authors.initials: N
authors.lastname: Kubben
authors.affiliation: National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Oberdoerffer
authors.affiliation: National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD, USA viveksharmabt@gmail.com mistelit@mail.nih.gov.
authors.forename: Tom
authors.initials: T
authors.lastname: Misteli
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism*; D049109:Cell Proliferation; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D019398:Genes, BRCA1; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D046228:Microarray Analysis; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C475078:HNRNPUL1 protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors
keywords: BRCA1; RAP80; hnRNPUL1; p53; repair