S-phase PARylation of microprotein RSMC enhances the function of Sororin in sister chromatid cohesion
Jiang M. Zhang J. He J. Miao Y. Wang L. Zhong H. Gong Y. Li Z. Du L.-L. Xu X. Chen C. Ydyrys A. Xia Y. Cao Q. Lou H. Hou W.
2 January 2026Springer Science and Business Media Deutschland GmbH
EMBO Journal
2026#45Issue 1278 - 309 pp.
Sororin is essential for establishing sister chromatid cohesion concurrently with DNA replication in metazoans. Although acetylation of the cohesin subunit SMC3 by ESCO1/2 is necessary for Sororin recruitment, it is by itself not sufficient. Here, we demonstrate that DNA replication-coupled Poly(ADP-Ribose) Polymerase (PARP) activity is an additional prerequisite in human cells. During normal S-phase, PARP1 PARylates a microprotein encoded by the alternative ORF C11ORF98, which we designate RSMC (28S rRNA/ribosome and Sororin micro-cofactor). This PARylation strengthens the interaction of RSMC with Sororin, enhancing both chromatin recruitment and anti-Wapl activity of Sororin in concert with SMC3 acetylation. Notably, overexpression of RSMC is able to rescue cohesion defects induced by the PARP inhibitor olaparib. These findings highlight understudied microproteins as critical regulators of fundamental cellular processes, such as sister chromatid cohesion.
Chromatin , Cohesin , Dark Proteome , DNA Replication , Microprotein
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Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China
State Key Laboratory of Plant Environmental Resilience, College of Biological Sciences, China Agricultural University, Beijing, 100193, China
State Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, 100084, China
National Institute of Biological Sciences, Beijing, China
Biomedical Research Centre, Al-Farabi Kazakh National University, Al-Farabi Avenue 71, Almaty, 050038, Kazakhstan
Guangdong Key Laboratory for Genome Stability & Disease Prevention
State Key Laboratory of Plant Environmental Resilience
State Key Laboratory of Membrane Biology
National Institute of Biological Sciences
Biomedical Research Centre
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