Checkpoint functions of RecQ helicases at perturbed DNA replication fork

Ahamad, Nafees; Khan, Saman; Mahdi, Alaa Taha A.; Xu, Yongjie

doi:10.1007/s00294-020-01147-y

Cited by 3 publications

(1 citation statement)

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“…It has been shown that this helicase removes Rad51 filaments and facilitates the access of nucleases for the processing of stalled forks to trigger DNA repair (Di Marco et al 2017 ; Hu et al 2007 ). Thus, apart from the role of RECQL5 in transcription, a putative role in replication or DNA repair is yet unclear (Ahamad et al 2021 ; Hamadeh and Lansdorp 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

Lafuente-Barquero,

Svejstrup,

Luna

et al. 2024

Mol Genet Genomics

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RECQL5 is a member of the conserved RecQ family of DNA helicases involved in the maintenance of genome stability that is specifically found in higher eukaryotes and associates with the elongating RNA polymerase II. To expand our understanding of its function we expressed human RECQL5 in the yeast Saccharomyces cerevisiae, which does not have a RECQL5 ortholog. We found that RECQL5 expression leads to cell growth inhibition, increased genotoxic sensitivity and transcription-associated hyperrecombination. Chromatin immunoprecipitation and transcriptomic analysis of yeast cells expressing human RECQL5 shows that this is recruited to transcribed genes and although it causes only a weak impact on gene expression, in particular at G + C-rich genes, it leads to a transcription termination defect detected as readthrough transcription. The data indicate that the interaction between RNAPII and RECQL5 is conserved from yeast to humans. Unexpectedly, however, the RECQL5-ID mutant, previously shown to have reduced the association with RNAPII in vitro, associates with the transcribing polymerase in cells. As a result, expression of RECQL5-ID leads to similar although weaker phenotypes than wild-type RECQL5 that could be transcription-mediated. Altogether, the data suggests that RECQL5 has the intrinsic ability to function in transcription-dependent and independent genome dynamics in S. cerevisiae.

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Section: Introductionmentioning

confidence: 99%

Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

Lafuente-Barquero,

Svejstrup,

Luna

et al. 2024

Mol Genet Genomics

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Smc5/6 Complex Promotes Rad3^ATR Checkpoint Signaling at the Perturbed Replication Fork through Sumoylation of the RecQ Helicase Rqh1

Khan

Ahamad

Bhadra

et al. 2022

Molecular and Cellular Biology

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Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?

2021

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DNA damage repair response is an important biological process involved in maintaining the fidelity of the genome in eukaryotes and prokaryotes. Several proteins that play a key role in this process have been identified. Alterations in these key proteins have been linked to different diseases including cancer. BLM is a 3′−5′ ATP-dependent RecQ DNA helicase that is one of the most essential genome stabilizers involved in the regulation of DNA replication, recombination, and both homologous and non-homologous pathways of double-strand break repair. BLM structure and functions are known to be conserved across many species like yeast, Drosophila, mouse, and human. Genetic mutations in the BLM gene cause a rare, autosomal recessive disorder, Bloom syndrome (BS). BS is a monogenic disease characterized by genomic instability, premature aging, predisposition to cancer, immunodeficiency, and pulmonary diseases. Hence, these characteristics point toward BLM being a tumor suppressor. However, in addition to mutations, BLM gene undergoes various types of alterations including increase in the copy number, transcript, and protein levels in multiple types of cancers. These results, along with the fact that the lack of wild-type BLM in these cancers has been associated with increased sensitivity to chemotherapeutic drugs, indicate that BLM also has a pro-oncogenic function. While a plethora of studies have reported the effect of BLM gene mutations in various model organisms, there is a dearth in the studies undertaken to investigate the effect of its oncogenic alterations. We propose to rationalize and integrate the dual functions of BLM both as a tumor suppressor and maybe as a proto-oncogene, and enlist the plausible mechanisms of its deregulation in cancers.

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Checkpoint functions of RecQ helicases at perturbed DNA replication fork

Cited by 3 publications

References 143 publications

Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

Smc5/6 Complex Promotes Rad3^ATR Checkpoint Signaling at the Perturbed Replication Fork through Sumoylation of the RecQ Helicase Rqh1

Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?

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Checkpoint functions of RecQ helicases at perturbed DNA replication fork

Cited by 3 publications

References 143 publications

Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

Smc5/6 Complex Promotes Rad3ATR Checkpoint Signaling at the Perturbed Replication Fork through Sumoylation of the RecQ Helicase Rqh1

Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword?

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Smc5/6 Complex Promotes Rad3^ATR Checkpoint Signaling at the Perturbed Replication Fork through Sumoylation of the RecQ Helicase Rqh1