Nej1 interacts with Sae2 at DNA double-stranded breaks to inhibit DNA resection.
Saved in:
| Title: | Nej1 interacts with Sae2 at DNA double-stranded breaks to inhibit DNA resection. |
|---|---|
| Authors: | Mojumdar, Aditya1, Adam, Nancy1, Cobb, Jennifer A.1 jcobb@ucalgary.ca |
| Source: | Journal of Biological Chemistry. Jun2022, Vol. 298 Issue 6, p1-13. 13p. |
| Subjects: | Double-strand DNA breaks, DNA helicases |
| Abstract: | The two major pathways of DNA double-strand break repair, nonhomologous end-joining and homologous recombination, are highly conserved from yeast to mammals. The regulation of 50-DNA resection controls repair pathway choice and influences repair outcomes. Nej1 was first identified as a canonical NHEJ factor involved in stimulating the ligation of broken DNA ends, and more recently, it was shown to participate in DNA end-bridging and in the inhibition of 50-resection mediated by the nuclease/helicase complex Dna2–Sgs1. Here, we show that Nej1 interacts with Sae2 to impact DSB repair in three ways. First, we show that Nej1 inhibits interaction of Sae2 with the Mre11–Rad50–Xrs2 complex and Sae2 localization to DSBs. Second, we found that Nej1 inhibits Sae2-dependent recruitment of Dna2 independently of Sgs1. Third, we determined that NEJ1 and SAE2 showed an epistatic relationship for end-bridging, an event that restrains broken DNA ends and reduces the frequency of genomic deletions from developing at the break site. Finally, we demonstrate that deletion of NEJ1 suppressed the synthetic lethality of sae2Δ sgs1Δ mutants, and that triple mutant viability was dependent on Dna2 nuclease activity. Taken together, these findings provide mechanistic insight to how Nej1 functionality inhibits the initiation of DNA resection, a role that is distinct from its involvement in endjoining repair at DSBs. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: egs DbLabel: Engineering Source An: 158577295 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Nej1 interacts with Sae2 at DNA double-stranded breaks to inhibit DNA resection. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Mojumdar%2C+Aditya%22">Mojumdar, Aditya</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Adam%2C+Nancy%22">Adam, Nancy</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Cobb%2C+Jennifer+A%2E%22">Cobb, Jennifer A.</searchLink><relatesTo>1</relatesTo><i> jcobb@ucalgary.ca</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. Jun2022, Vol. 298 Issue 6, p1-13. 13p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Double-strand+DNA+breaks%22">Double-strand DNA breaks</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+helicases%22">DNA helicases</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The two major pathways of DNA double-strand break repair, nonhomologous end-joining and homologous recombination, are highly conserved from yeast to mammals. The regulation of 50-DNA resection controls repair pathway choice and influences repair outcomes. Nej1 was first identified as a canonical NHEJ factor involved in stimulating the ligation of broken DNA ends, and more recently, it was shown to participate in DNA end-bridging and in the inhibition of 50-resection mediated by the nuclease/helicase complex Dna2–Sgs1. Here, we show that Nej1 interacts with Sae2 to impact DSB repair in three ways. First, we show that Nej1 inhibits interaction of Sae2 with the Mre11–Rad50–Xrs2 complex and Sae2 localization to DSBs. Second, we found that Nej1 inhibits Sae2-dependent recruitment of Dna2 independently of Sgs1. Third, we determined that NEJ1 and SAE2 showed an epistatic relationship for end-bridging, an event that restrains broken DNA ends and reduces the frequency of genomic deletions from developing at the break site. Finally, we demonstrate that deletion of NEJ1 suppressed the synthetic lethality of sae2Δ sgs1Δ mutants, and that triple mutant viability was dependent on Dna2 nuclease activity. Taken together, these findings provide mechanistic insight to how Nej1 functionality inhibits the initiation of DNA resection, a role that is distinct from its involvement in endjoining repair at DSBs. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=158577295 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jbc.2022.101937 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 1 Subjects: – SubjectFull: Double-strand DNA breaks Type: general – SubjectFull: DNA helicases Type: general Titles: – TitleFull: Nej1 interacts with Sae2 at DNA double-stranded breaks to inhibit DNA resection. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Mojumdar, Aditya – PersonEntity: Name: NameFull: Adam, Nancy – PersonEntity: Name: NameFull: Cobb, Jennifer A. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2022 Type: published Y: 2022 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 298 – Type: issue Value: 6 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
