TY - JOUR
T1 - Reconstitution of anaphase DNA bridge recognition and disjunction
AU - Sarlós, Kata
AU - Biebricher, Andreas S.
AU - Bizard, Anna H.
AU - Bakx, Julia A.M.
AU - Ferreté-Bonastre, Anna G.
AU - Modesti, Mauro
AU - Paramasivam, Manikandan
AU - Yao, Qi
AU - Peterman, Erwin J.G.
AU - Wuite, Gijs J.L.
AU - Hickson, Ian D.
PY - 2018
Y1 - 2018
N2 - Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can only be visualized by detection of associated proteins such as PICH, BLM, topoisomerase IIIα, and RPA. However, it remains unknown how these proteins work together to promote UFB processing. We used a combination of ensemble biochemistry and new single-molecule assays to reconstitute key steps of UFB recognition and processing by these human proteins in vitro. We discovered characteristic patterns of hierarchical recruitment and coordinated biochemical activities that were specific for DNA structures modeling UFBs arising at either centromeres or common fragile sites. Our results describe a mechanistic model for how unresolved DNA replication structures are processed by DNA-structure-specific binding factors in mitosis to prevent pathological chromosome nondisjunction.
AB - Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can only be visualized by detection of associated proteins such as PICH, BLM, topoisomerase IIIα, and RPA. However, it remains unknown how these proteins work together to promote UFB processing. We used a combination of ensemble biochemistry and new single-molecule assays to reconstitute key steps of UFB recognition and processing by these human proteins in vitro. We discovered characteristic patterns of hierarchical recruitment and coordinated biochemical activities that were specific for DNA structures modeling UFBs arising at either centromeres or common fragile sites. Our results describe a mechanistic model for how unresolved DNA replication structures are processed by DNA-structure-specific binding factors in mitosis to prevent pathological chromosome nondisjunction.
U2 - 10.1038/s41594-018-0123-8
DO - 10.1038/s41594-018-0123-8
M3 - Journal article
C2 - 30177760
AN - SCOPUS:85052987271
SN - 1545-9993
VL - 25
SP - 868
EP - 876
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 9
ER -