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Series GSE178927 Query DataSets for GSE178927
Status Public on Aug 20, 2021
Title DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability
Organisms Homo sapiens; Mus musculus
Experiment type Other
Summary The DNA polymerase zeta (Polζ) plays a critical role in bypassing DNA damage. REV3L, the catalytic subunit of Polζ is also essential in mouse embryonic development and cell proliferation for reasons that remain incompletely understood. In this study, we reveal that REV3L protein interacts with heterochromatin components including repressive histone marks, and localizes in pericentromeric regions through direct interaction with HP1 dimer. We demonstrate that Polζ/REV3L ensures progression of replication forks through difficult-to-replicate pericentromeric heterochromatin, thereby preventing spontaneous DNA and chromosome break formation. We also find that Rev3l-deficient cells are compromised in the repair of heterochromatin-associated DSBs, eliciting deletions in late replicating regions. Lack of REV3L leads to further consequences that may be ascribed to heterochromatin replication-associated functions of Polζ, with a disruption of the temporal replication program at specific loci. This is correlated with changes in epigenetic landscape and transcriptional control of developmentally regulated genes. These results reveal a new function of Polζ in preventing chromosome instability during replication of hetero­chromatic regions.
Overall design Nascent-DNA from early S-phase versus nascent-DNA from late S-phase
Contributor(s) Ben Yamin B, Ahmed-Seghir S, Tomida J, Despras E, Pouvelle C, Iurchenko A, Goulas J, Corre R, Delacour Q, Droin N, Dessen P, Goidin D, Lange SS, Mitjavila-Garcia MT, Baldacci G, Nikolaev S, Cadoret JC, Woodand RD, Kannouche PL
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Submission date Jun 25, 2021
Last update date Aug 22, 2021
Contact name Jean-Charles Cadoret
Organization name CNRS/ Université de Paris
Street address 15 rue hélène Brion
City Paris
ZIP/Postal code 75013
Country France
Platforms (2)
GPL10123 Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version)
GPL10449 Agilent-027411 SurePrint G3 Mouse CGH Microarray 4x180K (Feature Number version)
Samples (6)
GSM5401039 MEF-Rev3+/+_p5
GSM5401040 MEF-Rev3+/+_p60
GSM5401041 MEF-Rev3-/-_p7
BioProject PRJNA741504

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Supplementary file Size Download File type/resource
GSE178927_RAW.tar 315.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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