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Cited by 12DNA Repair MechanismsDNA and Nucleic Acid ChemistryTelomeres, Telomerase, and Senescence

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Harmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sites

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Kumar, Niranjan, Taneja, Arushi, Ghosh, Meenakshi, Rothweiler, Ulli, Sundaresan, Nagalingam Ravi, Singh, Mahavir·2024·Nucleic Acids Research
DOI 10.1093/nar/gkad1208PMC PMC10853778

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Abstract

The regulator of telomere elongation helicase 1 (RTEL1) plays roles in telomere DNA maintenance, DNA repair, and genome stability by dismantling D-loops and unwinding G-quadruplex structures. RTEL1 comprises a helicase domain, two tandem harmonin homology domains 1&2 (HHD1 and HHD2), and a Zn2+-binding RING domain. In vitro D-loop disassembly by RTEL1 is enhanced in the presence of replication protein A (RPA). However, the mechanism of RTEL1 recruitment at non-telomeric D-loops remains unknown. In this study, we have unravelled a direct physical interaction between RTEL1 and RPA. Under DNA damage conditions, we showed that RTEL1 and RPA colocalise in the cell. Coimmunoprecipitation showed that RTEL1 and RPA interact, and the deletion of HHDs of RTEL1 significantly reduced this interaction. NMR chemical shift perturbations (CSPs) showed that RPA uses its 32C domain to interact with the HHD2 of RTEL1. Interestingly, HHD2 also interacted with DNA in the in vitro experiments. HHD2 structure was determined using X-ray crystallography, and NMR CSPs mapping revealed that both RPA 32C and DNA competitively bind to HHD2 on an overlapping surface. These results establish novel roles of accessory HHDs in RTEL1’s functions and provide mechanistic insights into the RPA-mediated recruitment of RTEL1 to DNA repair sites.

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Graphical Abstract CC BY · PubMed Central
Figure 1. RTEL1 directly interacts with RPA. (A) Domain organization of human RTEL1. HHD constructs used in this work are shown with domain boundaries. (B) Domain organization of human RPA trimeric complex (consisting of RPA70, RPA32, and RPA14). Various constructs of RPA used in this study are shown with their domain boundaries. (C) Whole-cell extracts of HEK293T cells overexpressing HA-tagged human RTEL1 were immunoprecipitated (IP) with mentioned antibodies. The immunocomplexes (upper panel) and input (bottom panel) were analysed through immunoblotting (IB) with indicated antibodies. (D) Representative immunofluorescence images showing co-localization of endogenous RTEL1 and RPA in the nucleus of HeLa cells. Cells were either left untreated (upper panel) or treated (bottom panel) with 2 mM Hydroxyurea (HU) for 48 h, paraformaldehyde-fixed, and immuno-stained for RTEL1 (green) and RPA (red). Nuclear DNA (blue) was counterstained with Hoechst 33342. (E) Representative immunoblot showing co-immunoprecipitation of RPA with HA-RTEL1 and HA-RTEL1-ΔHHD1+2 in the presence or absence of Benzonase. Whole-cell extracts of HEK293T cells, overexpressing HA-tagged human RTEL1 and its deletion construct RTEL1-ΔHHD1+2, were immunoprecipitated (IP) using an anti-HA antibody. The immunocomplexes (upper panel) and input (bottom panel) were treated overnight with Benzonase and analysed through immunoblotting (IB) with indicated antibodies. (F) Bar graph showing % interaction between RPA and HA-RTEL1-ΔHHD1+2, relative to RPA and HA-RTEL1-FL. Data represent mean ± SEM (n = 3) using paired two-tailed Student's t test. Asterisks were used to represent p-values: ** P ≤ 0.01. (G) Bar graph showing % nuclei with more than or less than 30 γH2AX foci in U2OS cells (n = 160) overexpressing HA-RTEL1-FL and HA-RTEL1-ΔHHD1+2 under the background of siRNA mediated knockdown of endogenous RTEL1. Cells were cultured in the presence of 3 mM Hydroxyurea (HU) for 24 h and paraformaldehyde fixed. γH2AX foci were detected by immunofluorescence.
Figure 1. RTEL1 directly interacts with RPA. (A) Domain organization of human RTEL1. HHD constructs used in this work are shown with domain boundaries. (B) Domain organization of human RPA trimeric complex (consisting of RPA70, RPA32, and RPA14). Various constructs of RPA used in this study are shown with their domain boundaries. (C) Whole-cell extracts of HEK293T cells overexpressing HA-tagged human RTEL1 were immunoprecipitated (IP) with mentioned antibodies. The immunocomplexes (upper panel) and input (bottom panel) were analysed through immunoblotting (IB) with indicated antibodies. (D) Representative immunofluorescence images showing co-localization of endogenous RTEL1 and RPA in the nucleus of HeLa cells. Cells were either left untreated (upper panel) or treated (bottom panel) with 2 mM Hydroxyurea (HU) for 48 h, paraformaldehyde-fixed, and immuno-stained for RTEL1 (green) and RPA (red). Nuclear DNA (blue) was counterstained with Hoechst 33342. (E) Representative immunoblot showing co-immunoprecipitation of RPA with HA-RTEL1 and HA-RTEL1-ΔHHD1+2 in the presence or absence of Benzonase. Whole-cell extracts of HEK293T cells, overexpressing HA-tagged human RTEL1 and its deletion construct RTEL1-ΔHHD1+2, were immunoprecipitated (IP) using an anti-HA antibody. The immunocomplexes (upper panel) and input (bottom panel) were treated overnight with Benzonase and analysed through immunoblotting (IB) with indicated antibodies. (F) Bar graph showing % interaction between RPA and HA-RTEL1-ΔHHD1+2, relative to RPA and HA-RTEL1-FL. Data represent mean ± SEM (n = 3) using paired two-tailed Student's t test. Asterisks were used to represent p-values: ** P ≤ 0.01. (G) Bar graph showing % nuclei with more than or less than 30 γH2AX foci in U2OS cells (n = 160) overexpressing HA-RTEL1-FL and HA-RTEL1-ΔHHD1+2 under the background of siRNA mediated knockdown of endogenous RTEL1. Cells were cultured in the presence of 3 mM Hydroxyurea (HU) for 24 h and paraformaldehyde fixed. γH2AX foci were detected by immunofluorescence.CC BY · PubMed Central
Figure 2. NMR titration of RTEL1 HHD2 and RPA 32C domains. (A) Overlay of 1H-15N HSQC spectra of 15N-labelled HHD2 in the absence (black) and presence (red) of RPA 32C (at 1:4 molar ratio). Residues that showed large chemical shift perturbations (CSPs) are labelled. (B) 1H-15N cross-peaks trajectory of representative residues S1061, R1068, G1075 and A1081 of HHD2 upon titration with RPA 32C at indicated molar ratios. (C) Overlay of 1H -15N HSQC spectra of 15N-labelled 32C in the absence (black) and presence (red) of HHD2 (at 1:4 molar ratio). Residues that showed large CSPs are labelled. (D) 1H–15N cross-peaks trajectory of representative residues E223, T258, V259, and H263 of 32C upon titration with HHD2 at indicated molar ratios. (E) 2D line shape analysis of the interaction of HHD2 with 32C using NMR TITAN software. Observed and fitted spectral regions (zoomed in) are shown with indicated molar ratio of HHD2 and 32C at each titration step. 12 residues/spins (out of total 15 spins used for the analysis) along with the Fitted Kd is mentioned on the spectra. (F) Three-dimensional overlay of observed (gray) and fitted (magenta) peak of a representative spin R1068 to show quality of the fit. Total concentration of HHD2 and 32C are mentioned at each step of titration.
Figure 2. NMR titration of RTEL1 HHD2 and RPA 32C domains. (A) Overlay of 1H-15N HSQC spectra of 15N-labelled HHD2 in the absence (black) and presence (red) of RPA 32C (at 1:4 molar ratio). Residues that showed large chemical shift perturbations (CSPs) are labelled. (B) 1H-15N cross-peaks trajectory of representative residues S1061, R1068, G1075 and A1081 of HHD2 upon titration with RPA 32C at indicated molar ratios. (C) Overlay of 1H -15N HSQC spectra of 15N-labelled 32C in the absence (black) and presence (red) of HHD2 (at 1:4 molar ratio). Residues that showed large CSPs are labelled. (D) 1H–15N cross-peaks trajectory of representative residues E223, T258, V259, and H263 of 32C upon titration with HHD2 at indicated molar ratios. (E) 2D line shape analysis of the interaction of HHD2 with 32C using NMR TITAN software. Observed and fitted spectral regions (zoomed in) are shown with indicated molar ratio of HHD2 and 32C at each titration step. 12 residues/spins (out of total 15 spins used for the analysis) along with the Fitted Kd is mentioned on the spectra. (F) Three-dimensional overlay of observed (gray) and fitted (magenta) peak of a representative spin R1068 to show quality of the fit. Total concentration of HHD2 and 32C are mentioned at each step of titration.CC BY · PubMed Central
Figure 3. Structure of HHD2 domain of RTEL1. (A) Multiple sequence alignment of HHD2 of RTEL1 proteins from different vertebrate species. The secondary structure corresponding to the HHD2 of human RTEL1 is depicted at the top (green ribbon). The consensus sequence, including the conserved residues (red), is shown at the bottom. (B) Crystal structure of HHD2 domain of human RTEL1. Sidechains of evolutionarily conserved residues are shown as stick models (fully conserved residues and partially conserved residues are shown in red and gold, respectively). (C) Electron density map of a representative region consisting of conserved residues Y1086, D1090, R1121, H1123, and H1124. One salt bridge (D1090 OD1–R1121 NH1) and two H-bonds (Y1086 OH–H1124 ND1 and D1090 OD2–H1123 NE2) are shown (red dash line). (D) Surface electrostatic potential map of HHD2. One side (consisting of H1, H2, and H4 helices) of the protein has positively charged surface (blue), while the other side (consisting of H2, H3, and H5 helices) has negatively charged surface (red).
Figure 3. Structure of HHD2 domain of RTEL1. (A) Multiple sequence alignment of HHD2 of RTEL1 proteins from different vertebrate species. The secondary structure corresponding to the HHD2 of human RTEL1 is depicted at the top (green ribbon). The consensus sequence, including the conserved residues (red), is shown at the bottom. (B) Crystal structure of HHD2 domain of human RTEL1. Sidechains of evolutionarily conserved residues are shown as stick models (fully conserved residues and partially conserved residues are shown in red and gold, respectively). (C) Electron density map of a representative region consisting of conserved residues Y1086, D1090, R1121, H1123, and H1124. One salt bridge (D1090 OD1–R1121 NH1) and two H-bonds (Y1086 OH–H1124 ND1 and D1090 OD2–H1123 NE2) are shown (red dash line). (D) Surface electrostatic potential map of HHD2. One side (consisting of H1, H2, and H4 helices) of the protein has positively charged surface (blue), while the other side (consisting of H2, H3, and H5 helices) has negatively charged surface (red).CC BY · PubMed Central
Figure 4. The binding interface of RTEL1-RPA interaction. (A) Quantitation of CSPs in HHD2 upon titration with RPA 32C (at 1:4 molar ratio). Residues with more than average CSP (green dash line) are marked as an orange bar and considered as significantly perturbed residues. Proline and unassigned residues are marked in blue. The secondary structure corresponding to HHD2 is shown at the top. (B) Significantly perturbed residues (orange) are marked on the structure of HHD2 (ribbon form on the left and surface form in the middle). Most of these residues lie on the positively charged surface (on the right) of HHD2. (C) Quantitation of CSPs in 32C upon titration with HHD2 (at 1:4 molar ratio). Residues with more than average CSP (green dash line) are marked as an orange bar and considered as significantly perturbed residues. Proline and unassigned residues are marked in blue. The secondary structure corresponding to 32C is shown at the top. (D) Significantly perturbed residues (orange) are marked on the structure of 32C (ribbon form - left and surface form - middle). Most of these residues lie on the negatively charged surface (right) of 32C. (E) HADDOCK model of RTEL1 HHD2–RPA 32C complex with several interface residues marked. Positively (blue) and negatively (red) charged interacting surfaces of HHD2 and 32C, respectively, are shown with dotted line (black) representing the interface.
Figure 4. The binding interface of RTEL1-RPA interaction. (A) Quantitation of CSPs in HHD2 upon titration with RPA 32C (at 1:4 molar ratio). Residues with more than average CSP (green dash line) are marked as an orange bar and considered as significantly perturbed residues. Proline and unassigned residues are marked in blue. The secondary structure corresponding to HHD2 is shown at the top. (B) Significantly perturbed residues (orange) are marked on the structure of HHD2 (ribbon form on the left and surface form in the middle). Most of these residues lie on the positively charged surface (on the right) of HHD2. (C) Quantitation of CSPs in 32C upon titration with HHD2 (at 1:4 molar ratio). Residues with more than average CSP (green dash line) are marked as an orange bar and considered as significantly perturbed residues. Proline and unassigned residues are marked in blue. The secondary structure corresponding to 32C is shown at the top. (D) Significantly perturbed residues (orange) are marked on the structure of 32C (ribbon form - left and surface form - middle). Most of these residues lie on the negatively charged surface (right) of 32C. (E) HADDOCK model of RTEL1 HHD2–RPA 32C complex with several interface residues marked. Positively (blue) and negatively (red) charged interacting surfaces of HHD2 and 32C, respectively, are shown with dotted line (black) representing the interface.CC BY · PubMed Central
Figure 5. 32C–HHD2 Interaction surface validation through site-directed mutagenesis of HHD2 residues. (A) 3D bar plot showing quantitation of CSPs in 32C upon titration with HHD2 WT (red), HHD2 H1058E (green), HHD2 R1068A (magenta), HHD2 R1068E (blue) and HHD2 K1087E (orange) (all at 1:2 molar ratio). (B) 1H–15N cross-peaks trajectory of representative residues (black) E223, Y256, T258 and D268 of 32C upon titration with wild type (red) and different mutants (green, magenta, blue, and orange) of HHD2 at 1:2 molar ratio. CSPs of each representative residues of 32C are shown for titration with all four mutants of HHD2. In each inset, CSP with wild type (WT) HHD2 is shown for comparison.
Figure 5. 32C–HHD2 Interaction surface validation through site-directed mutagenesis of HHD2 residues. (A) 3D bar plot showing quantitation of CSPs in 32C upon titration with HHD2 WT (red), HHD2 H1058E (green), HHD2 R1068A (magenta), HHD2 R1068E (blue) and HHD2 K1087E (orange) (all at 1:2 molar ratio). (B) 1H–15N cross-peaks trajectory of representative residues (black) E223, Y256, T258 and D268 of 32C upon titration with wild type (red) and different mutants (green, magenta, blue, and orange) of HHD2 at 1:2 molar ratio. CSPs of each representative residues of 32C are shown for titration with all four mutants of HHD2. In each inset, CSP with wild type (WT) HHD2 is shown for comparison.CC BY · PubMed Central
Figure 6. NMR titration of HHD2 and ssDNA-22. (A) Overlay of 1H–15N HSQC spectra of HHD2 in the absence (black) and presence (red) of ssDNA-22 (at 1:2 molar ratio). Residues that showed large CSPs are labelled. (B) 1H–15N cross-peaks trajectory of representative residues R1068, G1075, L1080, and R1115 of HHD2 upon titration with ssDNA-22 at indicated molar ratios. (C) Quantitation of CSPs in HHD2 upon titration with ssDNA-22 (at 1:2 molar ratio). Residues that showed more than average CSP (green dash line) are marked as a pink bar and considered as significantly perturbed residues. Proline and unassigned residues are marked in blue. The secondary structure of HHD2 is shown at the top. (D) Significantly perturbed residues (pink) are marked on the structure of HHD2 (ribbon form on the left and surface form in the middle). Most of these residues lie on the positively charged surface (on the right) of HHD2. (E) 2D line shape analysis of the interaction of HHD2 with ssDNA-22 using NMR TITAN software. Observed and fitted spectral regions (zoomed in) are shown with indicated molar ratio of HHD2 and ssDNA-22 at each titration steps. Nine residues/spins (out of total 15 spins used for the analysis) along with the Fitted Kd is mentioned on the spectra. (F) Three-dimensional overlay of observed (gray) and fitted (magenta) peak of a representative spin R1115 to show quality of the fit. Total concentration of HHD2 and ssDNA-22 are mentioned at each step of titration.
Figure 6. NMR titration of HHD2 and ssDNA-22. (A) Overlay of 1H–15N HSQC spectra of HHD2 in the absence (black) and presence (red) of ssDNA-22 (at 1:2 molar ratio). Residues that showed large CSPs are labelled. (B) 1H–15N cross-peaks trajectory of representative residues R1068, G1075, L1080, and R1115 of HHD2 upon titration with ssDNA-22 at indicated molar ratios. (C) Quantitation of CSPs in HHD2 upon titration with ssDNA-22 (at 1:2 molar ratio). Residues that showed more than average CSP (green dash line) are marked as a pink bar and considered as significantly perturbed residues. Proline and unassigned residues are marked in blue. The secondary structure of HHD2 is shown at the top. (D) Significantly perturbed residues (pink) are marked on the structure of HHD2 (ribbon form on the left and surface form in the middle). Most of these residues lie on the positively charged surface (on the right) of HHD2. (E) 2D line shape analysis of the interaction of HHD2 with ssDNA-22 using NMR TITAN software. Observed and fitted spectral regions (zoomed in) are shown with indicated molar ratio of HHD2 and ssDNA-22 at each titration steps. Nine residues/spins (out of total 15 spins used for the analysis) along with the Fitted Kd is mentioned on the spectra. (F) Three-dimensional overlay of observed (gray) and fitted (magenta) peak of a representative spin R1115 to show quality of the fit. Total concentration of HHD2 and ssDNA-22 are mentioned at each step of titration.CC BY · PubMed Central
Figure 7. Isothermal titration calorimetry of HHD2 and DNA. The equilibrium Kd obtained upon fitting the raw data is mentioned in each panel. (A) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-6. No binding was observed between HHD2 and ssDNA-6. (B) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-12. (C) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-22. (D) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-24. (E) Raw and fitted ITC binding isotherms for the interaction of HHD2 with dsDNA-24. (F) Raw and fitted ITC binding isotherms for the interaction of HHD2 with 5′ss_dsDNA-24. (G) Raw and fitted ITC binding isotherms for the interaction of HHD2 with 3′ss_dsDNA-24.
Figure 7. Isothermal titration calorimetry of HHD2 and DNA. The equilibrium Kd obtained upon fitting the raw data is mentioned in each panel. (A) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-6. No binding was observed between HHD2 and ssDNA-6. (B) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-12. (C) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-22. (D) Raw and fitted ITC binding isotherms for the interaction of HHD2 with ssDNA-24. (E) Raw and fitted ITC binding isotherms for the interaction of HHD2 with dsDNA-24. (F) Raw and fitted ITC binding isotherms for the interaction of HHD2 with 5′ss_dsDNA-24. (G) Raw and fitted ITC binding isotherms for the interaction of HHD2 with 3′ss_dsDNA-24.CC BY · PubMed Central
Figure 8. The interplay among RTEL1 HHD2, RPA 32C and DNA. (A) A subset of significantly perturbed residues of HHD2 upon binding to only RPA 32C (orange), only ssDNA (pink), and both 32C and ssDNA (red) are shown in Venn diagram. One representative residue from each subset is denoted on the surface-filled structure of HHD2. (B) 1H–15N HSQC cross-peaks trajectory of representative residues R1068, A1081, and F1119 of HHD2 upon titration with RPA 32C and ssDNA-22 at indicated molar ratios are shown (left panel). Competitive NMR titration (right panel) of 15N-labelled HHD2 with RPA 32C and ssDNA are shown. Arrow (green and blue) indicates the direction of movement of the cross-peaks upon titration. Initial and final peak positions are indicated by dashed line (pink). NMR titration of the HHD2–32C complex with DNA showed that the cross-peak of A1081 comes back to the free HHD2/HHD2–DNA complex position while the cross-peaks of F1119 and R1068 follow the path towards the HHD2-DNA complex. (C) 1H–15N HSQC cross-peaks trajectory of representative residues R1068, A1081, F1119, L1064 and G1075 of HHD2 upon titration with ssDNA-22 and RPA 32C at indicated molar ratios (left panel). Competitive NMR titration (right panel) of 15N-labelled HHD2 with ssDNA and RPA 32C are shown. Arrow (green and blue) indicates the direction of movement of the cross-peaks upon titration. Initial and final peak positions are indicated by dashed line (pink). Green dotted line indicates final position of cross-peaks in ternary complex. NMR titration of the HHD2–DNA complex with 32C showed that the cross-peak of A1081 and R1068 comes back only half-way to the HHD2-32C complex position while cross-peaks of L1064, and G1075 do not show interaction with 32C. The cross-peak of F1119 remains almost at the HHD2-DNA complex position even after addition of six molar equivalents of 32C.
Figure 8. The interplay among RTEL1 HHD2, RPA 32C and DNA. (A) A subset of significantly perturbed residues of HHD2 upon binding to only RPA 32C (orange), only ssDNA (pink), and both 32C and ssDNA (red) are shown in Venn diagram. One representative residue from each subset is denoted on the surface-filled structure of HHD2. (B) 1H–15N HSQC cross-peaks trajectory of representative residues R1068, A1081, and F1119 of HHD2 upon titration with RPA 32C and ssDNA-22 at indicated molar ratios are shown (left panel). Competitive NMR titration (right panel) of 15N-labelled HHD2 with RPA 32C and ssDNA are shown. Arrow (green and blue) indicates the direction of movement of the cross-peaks upon titration. Initial and final peak positions are indicated by dashed line (pink). NMR titration of the HHD2–32C complex with DNA showed that the cross-peak of A1081 comes back to the free HHD2/HHD2–DNA complex position while the cross-peaks of F1119 and R1068 follow the path towards the HHD2-DNA complex. (C) 1H–15N HSQC cross-peaks trajectory of representative residues R1068, A1081, F1119, L1064 and G1075 of HHD2 upon titration with ssDNA-22 and RPA 32C at indicated molar ratios (left panel). Competitive NMR titration (right panel) of 15N-labelled HHD2 with ssDNA and RPA 32C are shown. Arrow (green and blue) indicates the direction of movement of the cross-peaks upon titration. Initial and final peak positions are indicated by dashed line (pink). Green dotted line indicates final position of cross-peaks in ternary complex. NMR titration of the HHD2–DNA complex with 32C showed that the cross-peak of A1081 and R1068 comes back only half-way to the HHD2-32C complex position while cross-peaks of L1064, and G1075 do not show interaction with 32C. The cross-peak of F1119 remains almost at the HHD2-DNA complex position even after addition of six molar equivalents of 32C.CC BY · PubMed Central
Figure 9. Proposed model of RPA mediated recruitment of RTEL1 at DNA repair sites. Prolonged replication block by hydroxyurea treatment eventually leads to DNA double-strand break (DSB). MRN/Exo1 (pink) complex executes 5′ end resection to generate the 3′ overhang, which quickly gets coated by RPA (red). RAD51 (cyan) nucleoprotein filament invades the homologous dsDNA to form D (displacement)-loop. RAD54 (grey) translocase activity helps in the removal of RAD51. RPA, present on the displaced ssDNA and invading strand, potentially will recruit the RTEL1 (green) on D-loop through its 32C domain. The 5′-3′ helicase activity of RTEL1 helps disassemble the D-loop. It thus directs the recombination intermediate to follow the synthesis-dependent strand-annealing (SDSA) pathway of homologous recombination to generate the non-crossover products.
Figure 9. Proposed model of RPA mediated recruitment of RTEL1 at DNA repair sites. Prolonged replication block by hydroxyurea treatment eventually leads to DNA double-strand break (DSB). MRN/Exo1 (pink) complex executes 5′ end resection to generate the 3′ overhang, which quickly gets coated by RPA (red). RAD51 (cyan) nucleoprotein filament invades the homologous dsDNA to form D (displacement)-loop. RAD54 (grey) translocase activity helps in the removal of RAD51. RPA, present on the displaced ssDNA and invading strand, potentially will recruit the RTEL1 (green) on D-loop through its 32C domain. The 5′-3′ helicase activity of RTEL1 helps disassemble the D-loop. It thus directs the recombination intermediate to follow the synthesis-dependent strand-annealing (SDSA) pathway of homologous recombination to generate the non-crossover products.CC BY · PubMed Central

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Metadata

Authors
Kumar, N., Taneja, A., Ghosh, M., Rothweiler, U., Sundaresan, N. R., & Singh, M.
Affiliations
  • Indian Institute of Science Bangalore (IN)
  • UiT The Arctic University of Norway (NO)
Corresponding author
Singh, Mahavir
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2023-12-28
Volume
52
Issue
3
Pages
1450-1470
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkad1208
PMC
PMC10853778
OpenAlex
W4390311654
Cited by
12
References
77
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 1
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) (acceptedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • Department of Biotechnology (BT/PR15829/BRB/10/1469/2015)
  • Ramalingaswami Fellowship (BT/RLF/Re-entry/23/2013, STR/2021/000 015)
  • Science and Engineering Research Board
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords
RTEL1, RPA, DNA repair, telomere maintenance, protein-DNA interactions, protein-protein interaction, RING domain, DNA damage response, genome stability
MeSH terms
DNA, DNA Repair, DNA Replication, DNA Helicases, Humans, Telomere, Replication Protein A

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Kumar, N., Taneja, A., Ghosh, M., Rothweiler, U., Sundaresan, N. R., & Singh, M. (2024). Harmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sites. Nucleic Acids Research. https://doi.org/10.1093/nar/gkad1208

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