Repair Of DNA Double-Strand Breaks By Non-Homologous End-Joining Is Independent Of Cisplatin-Induced Checkpoint Activation And Downstream Damage Response Pathways In A Non-Small Cell Lung Cancer Cell Culture Model

End Joining ◽

Strand Breaks ◽

Dna Double Strand Break ◽

Damage Response ◽

Non Coding Rnas ◽

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer.  Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs.  Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated.  This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs

Molecules ◽

10.3390/molecules23112789 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2789 ◽

Cited By ~ 24

Author(s):

Roopa Thapar

Keyword(s):

Strand Break ◽

Double Strand Breaks ◽

End Joining ◽

Strand Breaks ◽

Dna Double Strand Break ◽

Damage Response ◽

Non Coding Rnas ◽

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair.

Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs

10.20944/preprints201810.0500.v3 ◽

2018 ◽

Author(s):

Roopa Thapar

Keyword(s):

Strand Break ◽

Double Strand Breaks ◽

End Joining ◽

Strand Breaks ◽

Dna Double Strand Break ◽

Damage Response ◽

Non Coding Rnas ◽

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer.  Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs.  Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated.  This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs

10.20944/preprints201810.0500.v2 ◽

2018 ◽

Author(s):

Roopa Thapar

Keyword(s):

Strand Break ◽

Double Strand Breaks ◽

End Joining ◽

Strand Breaks ◽

Dna Double Strand Break ◽

Damage Response ◽

Non Coding Rnas ◽

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer.  Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs.  Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated.  This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation

Nucleic Acids Research ◽

10.1093/nar/gkz263 ◽

2019 ◽

Vol 47 (12) ◽

pp. 6236-6249 ◽

Cited By ~ 9

Author(s):

Kirk L West ◽

Jessica L Kelliher ◽

Zhanzhan Xu ◽

Liwei An ◽

Megan R Reed ◽

...

Keyword(s):

Dna Damage ◽

Double Strand Breaks ◽

Parp Inhibition ◽

Current Evidence ◽

Dependent Manner ◽

End Joining ◽

Checkpoint Activation ◽

Strand Breaks ◽

Abstract The tumor suppressor protein 53BP1 plays key roles in response to DNA double-strand breaks (DSBs) by serving as a master scaffold at the damaged chromatin. Current evidence indicates that 53BP1 assembles a cohort of DNA damage response (DDR) factors to distinctly execute its repertoire of DSB responses, including checkpoint activation and non-homologous end joining (NHEJ) repair. Here, we have uncovered LC8 (a.k.a. DYNLL1) as an important 53BP1 effector. We found that LC8 accumulates at laser-induced DNA damage tracks in a 53BP1-dependent manner and requires the canonical H2AX-MDC1-RNF8-RNF168 signal transduction cascade. Accordingly, genetic inactivation of LC8 or its interaction with 53BP1 resulted in checkpoint defects. Importantly, loss of LC8 alleviated the hypersensitivity of BRCA1-depleted cells to ionizing radiation and PARP inhibition, highlighting the 53BP1-LC8 module in counteracting BRCA1-dependent functions in the DDR. Together, these data establish LC8 as an important mediator of a subset of 53BP1-dependent DSB responses.

Recruitment of MRE-11 to complex DNA damage is modulated by meiosis-specific chromosome organization

10.1101/2020.06.26.174573 ◽

2020 ◽

Author(s):

Kailey Harrell ◽

Madison Day ◽

Sarit Smolikove

Keyword(s):

Dna Damage ◽

Double Strand Breaks ◽

End Joining ◽

Strand Breaks ◽

Damage Response ◽

Non Homologous End Joining ◽

Altered Form ◽

Laser Microirradiation ◽

Clustered Dna Damage

AbstractDNA double-strand breaks (DSBs) are one of the most dangerous assaults on the genome, and yet their natural and programmed production are inherent to life. When DSBs arise close together (clustered) they are particularly deleterious, and their repair may require an altered form of the DNA damage response. Our understanding of how clustered DSBs are repaired in the germline is unknown. Using UV laser microirradiation, we examine early events in the repair of clustered DSBs in germ cells within whole, live, Caenorhabditis elegans. We use precise temporal resolution to show how the recruitment of MRE-11 to complex damage is regulated, and that clustered DNA damage can recruit proteins from various repair pathways. Abrogation of non-homologous end joining or COM-1 attenuates the recruitment of MRE-11 through distinct mechanisms. The synaptonemal complex plays both positive and negative regulatory roles in these mutant contexts. These findings together indicate that MRE-11 is regulated by modifying its accessibility to chromosomes.