Dixit, S and Nagraj, T and Bhattacharya, D and Saxena, S and Sahoo, S and Chittela, RK and Somyajit, K and Nagaraju, G (2024) RTEL1 helicase counteracts RAD51-mediated homologous recombination and fork reversal to safeguard replicating genomes. In: Cell Reports, 43 (8).
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Abstract
Homologous recombination (HR) plays an essential role in the repair of DNA double-strand breaks (DSBs), replication stress responses, and genome maintenance. However, unregulated HR during replication can impair genome duplication and compromise genome stability. The mechanisms underlying HR regulation during DNA replication are obscure. Here, we find that RTEL1 helicase, RAD51, and RAD51 paralogs are enriched at stalled replication sites. The absence of RTEL1 leads to an increase in the RAD51-mediated HR and fork reversal during replication and affects genome-wide replication, which can be rescued by co-depleting RAD51 and RAD51 paralogs. Interestingly, co-depletion of fork remodelers such as SMARCAL1/ZRANB3/HLTF/FBH1 and expression of HR-defective RAD51 mutants also rescues replication defects in RTEL1-deficient cells. The anti-recombinase function of RTEL1 during replication depends on its interaction with PCNA and helicase activity. Together, our data identify the role of RTEL1 helicase in restricting RAD51-mediated fork reversal and HR activity to facilitate error-free genome duplication. © 2024 The Author(s)
| Item Type: | Journal Article |
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| Publication: | Cell Reports |
| Publisher: | Elsevier B.V. |
| Additional Information: | The copyright for this article belongs to the authors. |
| Keywords: | 4',6 diamidino 2 phenylindole; cycline; DNA binding protein; DNA helicase; doxribtimine; F box DNA helicase 1; green fluorescent protein; helicase; helicase like transcription factor; histone H2AX; hydroxyurea; oligonucleotide; polyvinylidene fluoride; protein p53; Rad51 protein; recombinant DNA; recombinant protein; recombinase; Regulator of telomere elongation helicase 1; short hairpin RNA; SMARCAL1; transcription factor; unclassified drug; zinc finger protein; ZRANB3, apoptosis; Article; Bradford assay; BrdU assay; carcinogenesis; cell cycle assay; cell division; cell survival; chromatin immunoprecipitation; comet assay; controlled study; DNA binding; DNA damage; DNA determination; DNA replication; DNA transfection; double stranded DNA break; flow cytometry; fluorescence activated cell sorting; fork reversal; gene expression; genetic transfection; genetic variability; genome; genomic instability; HeLa cell line; homologous recombination; human; human cell; immunoblotting; immunofluorescence; immunohistochemistry; immunoprecipitation; metaphase; MTT assay; mutant; polyacrylamide gel electrophoresis; protein expression; protein purification; real time polymerase chain reaction; sister chromatid; transcription elongation; U2OS cell line; Western blotting |
| Department/Centre: | Division of Biological Sciences > Biochemistry |
| Date Deposited: | 28 Aug 2024 10:53 |
| Last Modified: | 28 Aug 2024 10:53 |
| URI: | http://eprints.iisc.ac.in/id/eprint/86005 |
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