Biology subjects

Rybczynski, A. T.

Publications and source records attributed to Rybczynski, A. T..

2 recordsLinked to original sources

bioRxiv2026

A Distributed Architectural Code Governs DNA Repair

Repair of DNA double-strand breaks (DSBs) depends on large-scale changes in nuclear shape and genome organization. How damage signaling coordinates such remodeling remains unclear. We find that the human DNA damage response (DDR) couples interdependent, temporally ordered tubulin modifications to nuclear membrane and lipid regulation, driving nuclear reshaping (nucleomorphosis) through DSB-capturing nuclear envelope tubules (dsbNETs). Tubulin detyrosination by vasohibins 1/2 (VASH1/2) and acetylation by -tubulin acetyltransferase 1 (ATAT1) promote dsbNET formation and support both homologous recombination and non-homologous end joining. Microtubule-dependent processes also promote the phosphorylation-dependent inactivation of the membrane stress-sensing lipid regulator CTP cytidylyltransferase- (CCT), which typically restrains baseline nuclear lipid droplets (nLDs) and dsbNETs while supporting ATR signaling. Damage-induced nLD formation requires diacylglycerol acyltransferases 1/2 (DGAT1/2) and supports dsbNETs. Our findings reveal a distributed architectural code spanning interconnected cytoskeletal, membrane, and lipid regulators. This code governs nucleomorphosis and its role in DNA repair and genome stability.

molecular biology↗

bioRxiv2025

Cohesin drives chromatin scanning during the RAD51-mediated homology search.

Cohesin folds genomes into chromatin loops, whose roles are under debate. We report that double strand breaks (DSB) induce de novo formation of chromatin loops, with the break positioned at the loop base. These loops form only in S/G2 phases and occur during repair via homologous recombination (HR), concomitant with DNA end resection and RAD51 assembly. RAD51 showed two-tiered accumulation around DSBs, with a broad (~Mb) domain arising from the homology search. This domain is regulated by cohesin unloader, is constrained by TAD boundaries, and it overlaps with chromatin regions reeled through the break-anchored loop, suggesting that loop extrusion regulates the homology search. Indeed, depletion of NIPBL results in reduced HR, and this effect is more pronounced when the HR donor is far (~100 kb) from the break. Our data indicates that loop-extruding cohesin promotes the mammalian homology search by facilitating break-chromatin interactions within the damaged TAD. One-Sentence SummaryHigh spatiotemporal resolution analysis of double strand beak repair in 3D genome revealed the role of cohesin-driven loop extrusion in the homology search.

cell biology↗