The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery inS. pombe DOI Creative Commons
Alyssa Laffitte, Dongxu Lin, Yueming Tian

et al.

Published: April 18, 2025

Abstract While homologous recombination (HR) is often considered to be an error-free DNA repair mechanism in mitotically growing cells, the ultimate fidelity of this pathway depends on cell’s ability engage ideal template, replicated sister chromatid. This particularly challenging during repetitive regions genome for which non-allelic sequences can errantly used as templates. Here, we develop a model study spontaneous damage and that occurs at protein coding genes S. pombe flocculin family. We observe encoding most members family constitutively reside nuclear periphery by virtue their close proximity binding sites CENP-B like protein, Cbp1. Tethering via Cbp1 enhances stability against intragenic restrains intergenic between homeologous repeat-encoding sequences. In addition, LINC complex component Kms1, have previously shown associates with persistent double-strand breaks move periphery, also antagonizes both genes. Loss Kms1 use microhomology-mediated end-joining (MMEJ). Our observations suggest leverages compartmentalization maintain genic through constitutive tethering periphery. Moreover, association DSBs Kms1-containing complexes enforces stringency attenuate microhomology drives mutagenic or selecting correct template HR.

Language: Английский

The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery inS. pombe DOI Creative Commons
Alyssa Laffitte, Dongxu Lin, Yueming Tian

et al.

Published: April 18, 2025

Abstract While homologous recombination (HR) is often considered to be an error-free DNA repair mechanism in mitotically growing cells, the ultimate fidelity of this pathway depends on cell’s ability engage ideal template, replicated sister chromatid. This particularly challenging during repetitive regions genome for which non-allelic sequences can errantly used as templates. Here, we develop a model study spontaneous damage and that occurs at protein coding genes S. pombe flocculin family. We observe encoding most members family constitutively reside nuclear periphery by virtue their close proximity binding sites CENP-B like protein, Cbp1. Tethering via Cbp1 enhances stability against intragenic restrains intergenic between homeologous repeat-encoding sequences. In addition, LINC complex component Kms1, have previously shown associates with persistent double-strand breaks move periphery, also antagonizes both genes. Loss Kms1 use microhomology-mediated end-joining (MMEJ). Our observations suggest leverages compartmentalization maintain genic through constitutive tethering periphery. Moreover, association DSBs Kms1-containing complexes enforces stringency attenuate microhomology drives mutagenic or selecting correct template HR.

Language: Английский

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