DNA double-strand break end resection: a critical relay point for determining the pathway of repair and signaling

The fine tuning of the DNA double strand break repair pathway choice relies on different regulatory layers that respond to environmental and local cues. Among them, the presence of non-canonical nucleic acids structures seems to create challenges for the repair of nearby DNA double strand breaks. In this review, we focus on the recently published effects of G-quadruplexes and R-loops on DNA end resection and homologous recombination. Finally, we hypothesized a connection between those two atypical DNA structures in inhibiting the DNA end resection step of HR.

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Ctf4 Prevents Genome Rearrangements by Suppressing DNA Double-Strand Break Formation and Its End Resection at Arrested Replication Forks

Molecular Cell ◽

10.1016/j.molcel.2017.04.020 ◽

2017 ◽

Vol 66 (4) ◽

pp. 533-545.e5 ◽

Cited By ~ 20

Author(s):

Mariko Sasaki ◽

Takehiko Kobayashi

Keyword(s):

Strand Break ◽

Genome Rearrangements ◽

Double Strand Break ◽

Replication Forks ◽

Dna Double Strand Break ◽

End Resection ◽

Break Formation

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Multifunctional properties of Nej1XLF C-terminus promote end-joining and impact DNA double-strand break repair pathway choice

10.1101/2022.01.13.476264 ◽

2022 ◽

Author(s):

Aditya Mojumdar ◽

Nancy Adam ◽

Jennifer A Cobb

Keyword(s):

Strand Break ◽

Double Strand Break ◽

Repair Pathway ◽

End Joining ◽

C Terminus ◽

Dna Double Strand Break ◽

Canonical Pathways ◽

Pathway Choice ◽

Non Homologous End Joining ◽

End Resection

A DNA double strand break (DSB) is primarily repaired by one of two canonical pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ requires no or minimal end processing for ligation, whereas HR requires 5 end resection followed by a search for homology. The main event that determines the mode of repair is the initiation of 5 resection because if resection starts, then NHEJ cannot occur. Nej1 is a canonical NHEJ factor that functions at the cross-roads of repair pathway choice and prior to its function in stimulating Dnl4 ligase. Nej1 competes with Dna2, inhibiting its recruitment to DSBs and thereby inhibiting resection. The highly conserved C-terminal region (CTR) of Nej1 (330- 338) is important for two events that drive NHEJ, stimulating ligation and inhibiting resection, but it is dispensable for end-bridging. By combining nej1 point mutants with nuclease-dead dna2-1, we find that Nej1-F335 is essential for end-joining whereas V338 promotes NHEJ indirectly through inhibiting Dna2-mediated resection.

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Age-associated deficient recruitment of 53BP1 in G1 cells directs DNA double-strand break repair to BRCA1/CtIP-mediated DNA-end resection

Aging ◽

10.18632/aging.202419 ◽

2020 ◽

Author(s):

Teresa Anglada ◽

Anna Genescà ◽

Marta Martín

Keyword(s):

Strand Break ◽

Double Strand Break ◽

Double Strand Break Repair ◽

Dna Double Strand Break ◽

Break Repair ◽

Dna End Resection ◽

G1 Cells ◽

End Resection

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End resection: a key step in homologous recombination and DNA double-strand break repair

Genome Instability & Disease ◽

10.1007/s42764-020-00028-5 ◽

2020 ◽

Author(s):

Sijie Liu ◽

Daochun Kong

Keyword(s):

Homologous Recombination ◽

Strand Break ◽

Double Strand Break ◽

General Process ◽

Dna Double Strand Break ◽

Biochemical Mechanisms ◽

Strand Invasion ◽

Dna End Resection ◽

End Resection ◽

Made In

AbstractDNA end resection in eukaryotes is a key step in DNA homologous recombination (HR) and HR-mediated DNA double-strand break (DSB) repair, in which DNA2, EXO1 and MRE11 endo- and exonucleases remove several kilobases from the 5′ terminus of the DNA with DSB, while the 3′ terminus remains intact. The end resection-generated 3′ single-stranded DNA (ssDNA) overhang is then coated by RAD51 for subsequent strand invasion. In the last two decades, great progress has been made in understanding the biochemical mechanisms of end resection, including the identification of various enzymes involved in this process. However, some important questions about this process remain to be resolved. In this review, we summarize the general process of end resection and discuss the implications of the most recent findings for understanding of the end resection machinery.

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