Human RECQL5 participates in the removal of endogenous DNA damage

Human RECQL5 is a member of the RecQ helicase family, which maintains genome stability via participation in many DNA metabolic processes, including DNA repair. Human cells lacking RECQL5 display chromosomal instability. We find that cells depleted of RECQL5 are sensitive to oxidative stress, accumulate endogenous DNA damage, and increase the cellular poly(ADP-ribosyl)ate response. In contrast to the RECQ helicase family members WRN, BLM, and RECQL4, RECQL5 accumulates at laser-induced single-strand breaks in normal human cells. RECQL5 depletion affects the levels of PARP-1 and XRCC1, and our collective results suggest that RECQL5 modulates and/or directly participates in base excision repair of endogenous DNA damage, thereby promoting chromosome stability in normal human cells.

Download Full-text

The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease

Neural Plasticity ◽

10.1155/2016/3619274 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 28

Author(s):

Laura Narciso ◽

Eleonora Parlanti ◽

Mauro Racaniello ◽

Valeria Simonelli ◽

Alessio Cardinale ◽

...

Keyword(s):

Dna Damage ◽

Genome Stability ◽

Oxidative Dna Damage ◽

Excision Repair ◽

Strand Breaks ◽

Single Strand Breaks ◽

Age Related ◽

Neurological Alterations ◽

Base Excision ◽

And Function

There is a growing body of evidence indicating that the mechanisms that control genome stability are of key importance in the development and function of the nervous system. The major threat for neurons is oxidative DNA damage, which is repaired by the base excision repair (BER) pathway. Functional mutations of enzymes that are involved in the processing of single-strand breaks (SSB) that are generated during BER have been causally associated with syndromes that present important neurological alterations and cognitive decline. In this review, the plasticity of BER during neurogenesis and the importance of an efficient BER for correct brain function will be specifically addressed paying particular attention to the brain region and neuron-selectivity in SSB repair-associated neurological syndromes and age-related neurodegenerative diseases.

Download Full-text

Persistence of DNA Double-Strand Breaks in Normal Human Cells Induced by Radiation-Induced Bystander Effect

Radiation Research ◽

10.1667/rr2223.1 ◽

2011 ◽

Vol 175 (1) ◽

pp. 90-96 ◽

Cited By ~ 16

Author(s):

Mitsuaki Ojima ◽

Asahi Furutani ◽

Nobuhiko Ban ◽

Michiaki Kai

Keyword(s):

Bystander Effect ◽

Human Cells ◽

Double Strand Breaks ◽

Dna Double Strand Breaks ◽

Strand Breaks ◽

Radiation Induced ◽

Normal Human ◽

Normal Human Cells ◽

Radiation Induced Bystander Effect ◽

Persistence Of Dna

Download Full-text

Reduction of X-ray-induced DNA damage in normal human cells treated with the PrC-210 radioprotector

Biology Open ◽

10.1242/bio.035113 ◽

2018 ◽

Vol 7 (10) ◽

pp. bio035113 ◽

Cited By ~ 2

Author(s):

Michael Brand ◽

Matthias Sommer ◽

Frank Jermusek ◽

William E. Fahl ◽

Michael Uder

Keyword(s):

Dna Damage ◽

Human Cells ◽

X Ray ◽

Normal Human ◽

Normal Human Cells

Download Full-text

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector

Radiation Research ◽

10.1667/rr14928.1 ◽

2018 ◽

Vol 190 (2) ◽

pp. 133 ◽

Cited By ~ 2

Author(s):

Frank Jermusek ◽

Chelsea Benedict ◽

Emma Dreischmeier ◽

Michael Brand ◽

Michael Uder ◽

...

Keyword(s):

Dna Damage ◽

Human Cells ◽

Significant Suppression ◽

Ct Radiation ◽

Radiation Induced ◽

Normal Human ◽

Normal Human Cells

Download Full-text

DNA Damage and Repair in Rodent and Human Cells after Exposure to JANUS Fission Spectrum Neutrons: A Minor Fraction of Single-strand Breaks as Revealed by Alkaline Elution is Refractory to Repair

International Journal of Radiation Biology ◽

10.1080/09553008914550811 ◽

1989 ◽

Vol 55 (5) ◽

pp. 761-772 ◽

Cited By ~ 9

Author(s):

M.J. Peak ◽

J.G. Peak ◽

B.A. Carnes ◽

C.M. Chang Liu ◽

C.K. Hill

Keyword(s):

Dna Damage ◽

Human Cells ◽

Single Strand ◽

Alkaline Elution ◽

Dna Damage And Repair ◽

Strand Breaks ◽

Minor Fraction ◽

Fission Spectrum ◽

Single Strand Breaks ◽

A Minor

Download Full-text

Dissecting Highly Mutagenic Processing of Complex Clustered DNA Damage in Yeast Saccharomyces cerevisiae

Cells ◽

10.3390/cells10092309 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2309

Author(s):

Stanislav G. Kozmin ◽

Gregory Eot-Houllier ◽

Anne Reynaud-Angelin ◽

Didier Gasparutto ◽

Evelyne Sage

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Damage ◽

Excision Repair ◽

Cell Extract ◽

Yeast Saccharomyces Cerevisiae ◽

Strand Breaks ◽

High Mutation Frequency ◽

Base Excision ◽

Ionizing Radiation Exposure

Clusters of DNA damage, also called multiply damaged sites (MDS), are a signature of ionizing radiation exposure. They are defined as two or more lesions within one or two helix turns, which are created by the passage of a single radiation track. It has been shown that the clustering of DNA damage compromises their repair. Unresolved repair may lead to the formation of double-strand breaks (DSB) or the induction of mutation. We engineered three complex MDS, comprised of oxidatively damaged bases and a one-nucleotide (1 nt) gap (or not), in order to investigate the processing and the outcome of these MDS in yeast Saccharomyces cerevisiae. Such MDS could be caused by high linear energy transfer (LET) radiation. Using a whole-cell extract, deficient (or not) in base excision repair (BER), and a plasmid-based assay, we investigated in vitro excision/incision at the damaged bases and the mutations generated at MDS in wild-type, BER, and translesion synthesis-deficient cells. The processing of the studied MDS did not give rise to DSB (previously published). Our major finding is the extremely high mutation frequency that occurs at the MDS. The proposed processing of MDS is rather complex, and it largely depends on the nature and the distribution of the damaged bases relative to the 1 nt gap. Our results emphasize the deleterious consequences of MDS in eukaryotic cells.

Download Full-text

PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation

10.1101/243071 ◽

2018 ◽

Author(s):

George E. Ronson ◽

Ann Liza Piberger ◽

Martin R. Higgs ◽

Anna L. Olsen ◽

Grant S. Stewart ◽

...

Keyword(s):

Base Excision Repair ◽

Damage Tolerance ◽

Excision Repair ◽

Replication Forks ◽

Strand Breaks ◽

Single Strand Breaks ◽

Dna Base ◽

Repair Mechanisms ◽

Base Excision

AbstractPARP1 regulates the repair of DNA single strand breaks (SSBs) generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whilst PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication associated DNA damage due to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and through stabilising replication forks that encounter BER intermediates.

Download Full-text