ArticleNature communications2022
MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Immunohistochemical expression of JAK2, STAT3, POLH, UBE2T, and REV7 in serous ovarian carcinoma: clinicopathological associations and co-expression patterns.Journal of molecular histology · 2026Article
- Youthfulness of marrow AdipoqBone research · 2026Article
- Two Secondary Introductions From a Shared Bridgehead Population Show Evidence of Divergent and Parallel Selection.Molecular ecology · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- REV7 associates with ATRIP and inhibits ATR kinase activity.Nucleic acids research · 2026Article
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- A high-risk sepsis subtype identified by regulated cell death signatures and MAD2L2 validation.Frontiers in immunology · 2026Article
- The RING finger E3 ligase RNF25 protects DNA replication forks independently of its canonical roles in ubiquitin signaling.Nature communications · 2025Article
- Histone Lactylation Antagonizes Senescence and Skeletal Muscle Aging by Modulating Aging-Related Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.The Journal of biological chemistry · 2025Article
- DNA polymerase zeta can efficiently replicate structures formed by AT/TA repeat sequences and prevent their deletion.Nucleic acids research · 2025Article
- The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling.bioRxiv : the preprint server for biology · 2025Article
- Phylogenetic Relations and High-Altitude Adaptation in Wild Boar (Animals : an open access journal from MDPI · 2024Article
- A sophisticated mechanism governs Pol ζ activity in response to replication stress.Nature communications · 2024Article
- MAD2L2, a key regulator in ovarian cancer and promoting tumor progression.Scientific reports · 2024Article
- The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma.Journal of translational medicine · 2023Article
- REV7 Monomer Is Unable to Participate in Double Strand Break Repair and Translesion Synthesis but Suppresses Mitotic Errors.International journal of molecular sciences · 2023Article
- Dynamics of the DYNLL1-MRE11 complex regulate DNA end resection and recruitment of Shieldin to DSBs.Nature structural & molecular biology · 2023Article
- Quantification of Chromosomal Aberrations in Mammalian Cells.Bio-protocol · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protection of stalled replication forks is essential to prevent genome instability, a major driving force of tumorigenesis. Several key regulators of DNA double-stranded break (DSB) repair, including 53BP1 and RIF1, have been implicated in fork protection. MAD2L2, also known as REV7, plays an important role downstream of 53BP1/RIF1 by counteracting resection at DSBs in the recently discovered shieldin complex. The ability to bind and counteract resection at exposed DNA ends at DSBs makes MAD2L2/shieldin a prime candidate for also suppressing nucleolytic processing at stalled replication forks. However, the function of MAD2L2/shieldin outside of DNA repair is unknown. Here we address this by using genetic and single-molecule analyses and find that MAD2L2 is required for protecting and restarting stalled replication forks. MAD2L2 loss leads to uncontrolled MRE11-dependent resection of stalled forks and single-stranded DNA accumulation, which causes irreparable genomic damage. Unexpectedly, MAD2L2 limits resection at stalled forks independently of shieldin, since fork protection remained unaffected by shieldin loss. Instead, MAD2L2 cooperates with the DNA polymerases REV3L and REV1 to promote fork stability. Thus, MAD2L2 suppresses aberrant nucleolytic processing both at DSBs and stalled replication forks by differentially engaging shieldin and REV1/REV3L, respectively.
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