The Role of Blm Helicase in Homologous Recombination, Gene Conversion Tract Length, and Recombination Between Diverged Sequences in <i>Drosophila</i>  <i>melanogaster</i>

Ertl, Henry A; Russo, Daniel; Srivastava, Noori; Brooks, Joseph; Dao, Thu N; LaRocque, Jeannine R.

doi:10.1534/genetics.117.300285

Cited by 15 publications

(18 citation statements)

References 73 publications

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“…6a ). Most metazoan Bloom-like proteins lack a BDHCT domain and many, such as the Drosophila homolog, also lack a HRDC domain but are active in homologous recombination [ 62 ]. In A. vaga all five copies have an N-terminal RING-Ubox superfamily domain; the two pairs (B1,2 and C1,2) have the canonical RecQ family helicase domain while the fifth copy (A) has only the more general DEAD-like helicase superfamily domain in this region (Fig.…”

Section: Resultsmentioning

confidence: 99%

Evolutionary diversity and novelty of DNA repair genes in asexual Bdelloid rotifers

Hecox-Lea

Welch

2018

BMC Evol Biol

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BackgroundBdelloid rotifers are the oldest, most diverse and successful animal taxon for which males, hermaphrodites, and traditional meiosis are unknown. Their degenerate tetraploid genome, with 2–4 copies of most loci, includes thousands of genes acquired from all domains of life by horizontal transfer. Many bdelloid species thrive in ephemerally aquatic habitats by surviving desiccation at any life stage with no loss of fecundity or lifespan. Their unique genomic diversity and the intense selective pressure of desiccation provide an exceptional opportunity to study the evolution of diversity and novelty in genes involved in DNA repair.ResultsWe used genomic data and RNA-Seq of the desiccation process in the bdelloid Adineta vaga to characterize DNA damage reversal, translesion synthesis, and the major DNA repair pathways: base, nucleotide, and alternate excision repair, mismatch repair (MMR), and double strand break repair by homologous recombination (HR) and classical non-homologous end joining (NHEJ). We identify multiple horizontally transferred DNA damage response genes otherwise unknown in animals (AlkD, Fpg, LigK UVDE), and the presence of genes often considered vertebrate specific, particularly in the NHEJ complex and X family polymerases. While 75–100% of genes involved in MMR and HR are present in 0–2 copies, genes involved in NHEJ, which are present in only a single copy in nearly all other animals, are retained in 3–8 copies. We present structural predictions and expression evidence of neo- or sub-functionalization of multiple copy genes involved in NHEJ and other repair processes.ConclusionThe horizontally-acquired genes and duplicated genes in BER and NHEJ suggest resilience to oxidative damage is conferred in part by increased DNA damage recognition and efficient end repair capabilities. The pattern of gene loss and retention in MMR and HR may facilitate recombination and gene conversion between divergent sequences, thus providing at least some of the benefits of sex. The unique retention and divergence of duplicates genes in NHEJ may be facilitated by the lack of efficient selection in the absence of meiotic recombination and independent assortment, and may contribute to the evolutionary success of bdelloids.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1288-9) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Evolutionary diversity and novelty of DNA repair genes in asexual Bdelloid rotifers

Hecox-Lea

Welch

2018

BMC Evol Biol

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“…The previously characterized DR- white assay effectively measures intrachromosomal HR repair frequency in the Drosophila male premeiotic germline (Figure 1A)(Do et al 2014; Do and LaRocque 2015; Janssen et al 2016; Delabaere et al 2017; Ertl et al 2017). Briefly, flies containing the DR- white reporter assay and the I-SceI transgene are heat shocked to induce I-SceI expression in all cells, resulting in DSB formation followed by repair.…”

Section: Resultsmentioning

confidence: 99%

Chromosome Preference During Homologous Recombination Repair of DNA Double-Strand Breaks inDrosophila melanogaster

Fernandez¹,

Bloomer²,

Kellam³

et al. 2019

G3 Genes|Genomes|Genetics

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DNA double-strand breaks (DSBs) are especially toxic DNA lesions that, if left unrepaired, can lead to wide-ranging genomic instability. Of the pathways available to repair DSBs, the most accurate is homologous recombination (HR), where a homologous sequence is used as a donor template to restore genetic information at the break site. While much of the biochemical aspects of HR repair have been characterized, how the repair machinery locates and discriminates between potential homologous donor templates throughout the genome remains elusive. We use Drosophila melanogaster to investigate whether there is a preference between intrachromosomal and interhomolog donor sequences in mitotically dividing cells. Our results demonstrate that, although interhomolog HR is possible and frequent if another donor template is not available, intrachromosomal donor templates are highly preferred. This is true even if the interhomolog donor template is less diverged than the intrachromosomal donor template. Thus, despite the stringent requirements for homology, the chromosomal location of the donor template plays a more significant role in donor template choice.

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“…The Rad51-ssDNA complex is a right-handed helical polymer, with the DNA being held in an extended conformation [49]. The complex performs a "presynaptic" search for a homologous sequence in double-stranded DNA, leading to the production of heteroduplex DNA (hDNA) and the formation of a transient structure known as the displacement loop or D-loop structure [30,[48][49][50]. During homologous paring, the activity of Rad51 is stimulated by Rad 54, a member of the Swi2/Snf2 family of chromatin remodelling proteins/ATPases [48].…”

Section: Homologous Recombination Repairmentioning

confidence: 99%

“…After elongation, two pathways can be utilised to resolve the D-loop: the DSB repair (DSBR) and synthesis-dependent strand annealing (SDSA) models [30,49,50]. In the SDSA pathway, D-loop extension continues for a short distance.…”

Section: Homologous Recombination Repairmentioning

confidence: 99%

Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

Kryczka

Czarnecka-Chrebelska

et al. 2021

IJMS

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Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

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The Role of Blm Helicase in Homologous Recombination, Gene Conversion Tract Length, and Recombination Between Diverged Sequences in Drosophila melanogaster

Cited by 15 publications

References 73 publications

Evolutionary diversity and novelty of DNA repair genes in asexual Bdelloid rotifers

Evolutionary diversity and novelty of DNA repair genes in asexual Bdelloid rotifers

Chromosome Preference During Homologous Recombination Repair of DNA Double-Strand Breaks inDrosophila melanogaster

Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

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