Faculty Opinions recommendation of Nuclear dynamics of RAD52 group homologous recombination proteins in response to DNA damage.

SUMMARY Although homologous recombination and DNA repair phenomena in bacteria were initially extensively studied without regard to any relationship between the two, it is now appreciated that DNA repair and homologous recombination are related through DNA replication. In Escherichia coli, two-strand DNA damage, generated mostly during replication on a template DNA containing one-strand damage, is repaired by recombination with a homologous intact duplex, usually the sister chromosome. The two major types of two-strand DNA lesions are channeled into two distinct pathways of recombinational repair: daughter-strand gaps are closed by the RecF pathway, while disintegrated replication forks are reestablished by the RecBCD pathway. The phage λ recombination system is simpler in that its major reaction is to link two double-stranded DNA ends by using overlapping homologous sequences. The remarkable progress in understanding the mechanisms of recombinational repair in E. coli over the last decade is due to the in vitro characterization of the activities of individual recombination proteins. Putting our knowledge about recombinational repair in the broader context of DNA replication will guide future experimentation.

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Faculty Opinions recommendation of Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725315847.793503591 ◽

2015 ◽

Author(s):

Cheng-Ming Chiang

Keyword(s):

Dna Damage ◽

Homologous Recombination

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EXO1 Plays a Role in Generating Type I and Type II Survivors in Budding Yeast

Genetics ◽

10.1093/genetics/166.4.1641 ◽

2004 ◽

Vol 166 (4) ◽

pp. 1641-1649

Author(s):

Laura Maringele ◽

David Lydall

Keyword(s):

Homologous Recombination ◽

Budding Yeast ◽

Human Cells ◽

Telomere Maintenance ◽

Recombination Process ◽

Yeast Cells ◽

Type I ◽

Type Ii ◽

Recombination Proteins

Abstract Telomerase-defective budding yeast cells escape senescence by using homologous recombination to amplify telomeric or subtelomeric structures. Similarly, human cells that enter senescence can use homologous recombination for telomere maintenance, when telomerase cannot be activated. Although recombination proteins required to generate telomerase-independent survivors have been intensively studied, little is known about the nucleases that generate the substrates for recombination. Here we demonstrate that the Exo1 exonuclease is an initiator of the recombination process that allows cells to escape senescence and become immortal in the absence of telomerase. We show that EXO1 is important for generating type I survivors in yku70Δ mre11Δ cells and type II survivors in tlc1Δ cells. Moreover, in tlc1Δ cells, EXO1 seems to contribute to the senescence process itself.

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DNA damage-signaling, homologous recombination and genetic mutation induced by 5-azacytidine and DNA-protein crosslinks in Escherichia coli

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/j.mrfmmm.2021.111742 ◽

2021 ◽

pp. 111742

Author(s):

Julie A. Klaric ◽

David J. Glass ◽

Eli L. Perr ◽

Arianna D. Reuven ◽

Mason J. Towne ◽

...

Keyword(s):

Escherichia Coli ◽

Dna Damage ◽

Homologous Recombination ◽

Genetic Mutation ◽

Dna Damage Signaling ◽

Protein Crosslinks

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DHX9-dependent recruitment of BRCA1 to RNA promotes DNA end resection in homologous recombination

Nature Communications ◽

10.1038/s41467-021-24341-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Prasun Chakraborty ◽

Kevin Hiom

Keyword(s):

Dna Damage ◽

Homologous Recombination ◽

Rna Polymerase Ii ◽

Critical Role ◽

Dna Breaks ◽

Double Stranded Dna ◽

Recombination Repair ◽

Dna End Resection ◽

End Resection ◽

Rna Polymerase Ii Transcription

AbstractDouble stranded DNA Breaks (DSB) that occur in highly transcribed regions of the genome are preferentially repaired by homologous recombination repair (HR). However, the mechanisms that link transcription with HR are unknown. Here we identify a critical role for DHX9, a RNA helicase involved in the processing of pre-mRNA during transcription, in the initiation of HR. Cells that are deficient in DHX9 are impaired in the recruitment of RPA and RAD51 to sites of DNA damage and fail to repair DSB by HR. Consequently, these cells are hypersensitive to treatment with agents such as camptothecin and Olaparib that block transcription and generate DSB that specifically require HR for their repair. We show that DHX9 plays a critical role in HR by promoting the recruitment of BRCA1 to RNA as part of the RNA Polymerase II transcription complex, where it facilitates the resection of DSB. Moreover, defects in DHX9 also lead to impaired ATR-mediated damage signalling and an inability to restart DNA replication at camptothecin-induced DSB. Together, our data reveal a previously unknown role for DHX9 in the DNA Damage Response that provides a critical link between RNA, RNA Pol II and the repair of DNA damage by homologous recombination.

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