TY - JOUR
T1 - Multivalent interaction of ESCO2 with the replication machinery is required for sister chromatid cohesion in vertebrates
AU - Bender, Dawn
AU - Da Silva, Eulália Maria Lima
AU - Chen, Jingrong
AU - Poss, Annelise
AU - Gawey, Lauren
AU - Rulon, Zane
AU - Rankin, Susannah
N1 - Funding Information:
ACKNOWLEDGMENTS. This work was supported by NIH grant R01GM101250 and the Oklahoma Center for Adult Stem Cell Research, both to S.R.; a Pat and Don Capra Predoctoral Fellowship to D.B.; and a fellowship from the National Council for Scientific and Technological Development of Brazil (to E.M.L.D.S.). SPR analysis was performed at the Oklahoma Medical Research Foundation Biacore Facility, made possible by grant S10 OD025014-01. We are grateful to Padmaja Mehta-D’souza for assistance with SPR analysis, Paul Kaufman for providing the anti-PCNA antibody, Dean Dawson for careful review of the manuscript, and to all members of the Program in Cell Cycle and Cancer Biology for helpful discussions during the course of this work.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/1/14
Y1 - 2020/1/14
N2 - The tethering together of sister chromatids by the cohesin complex ensures their accurate alignment and segregation during cell division. In vertebrates, sister chromatid cohesion requires the activity of the ESCO2 acetyltransferase, which modifies the Smc3 subunit of cohesin. It was shown recently that ESCO2 promotes cohesion through interaction with the MCM replicative helicase. However, ESCO2 does not significantly colocalize with the MCM complex, suggesting there are additional interactions important for ESCO2 function. Here we show that ESCO2 is recruited to replication factories, sites of DNA replication, through interaction with PCNA. We show that ESCO2 contains multiple PCNA-interaction motifs in its N terminus, each of which is essential to its ability to establish cohesion. We propose that multiple PCNA-interaction motifs embedded in a largely flexible and disordered region of the protein underlie the unique ability of ESCO2 to establish cohesion between sister chromatids precisely as they are born during DNA replication.
AB - The tethering together of sister chromatids by the cohesin complex ensures their accurate alignment and segregation during cell division. In vertebrates, sister chromatid cohesion requires the activity of the ESCO2 acetyltransferase, which modifies the Smc3 subunit of cohesin. It was shown recently that ESCO2 promotes cohesion through interaction with the MCM replicative helicase. However, ESCO2 does not significantly colocalize with the MCM complex, suggesting there are additional interactions important for ESCO2 function. Here we show that ESCO2 is recruited to replication factories, sites of DNA replication, through interaction with PCNA. We show that ESCO2 contains multiple PCNA-interaction motifs in its N terminus, each of which is essential to its ability to establish cohesion. We propose that multiple PCNA-interaction motifs embedded in a largely flexible and disordered region of the protein underlie the unique ability of ESCO2 to establish cohesion between sister chromatids precisely as they are born during DNA replication.
KW - Chromosome biology
KW - Cohesin
KW - DNA replication
KW - Sister chromatid cohesion
UR - http://www.scopus.com/inward/record.url?scp=85077937511&partnerID=8YFLogxK
U2 - 10.1073/pnas.1911936117
DO - 10.1073/pnas.1911936117
M3 - Article
C2 - 31879348
AN - SCOPUS:85077937511
SN - 0027-8424
VL - 117
SP - 1081
EP - 1089
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
ER -