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10.3390/life11040267
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Article

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin

by
Serge Bauwens
1,
Liudmyla Lototska
1,†,
Stephane Koundrioukoff
2,
Michelle Debatisse
2,
Jing Ye
3,
Eric Gilson
1,3,* and
Aaron Mendez-Bermudez
1,3,*
1
Faculty of Medicine Nice, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, Université Côte d’Azur, 06107 Nice, France
2
Institut Gustave Roussy, Sorbonne Université, UPMC University, 94805 Villejuif, France
3
International Laboratory in Hematology, Cancer and Aging, Pôle Sino-Français de Recherches en Sciences du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
*
Authors to whom correspondence should be addressed.
†
Current address: Institute of Molecular Biology gGmbH (IMB), 55128 Mainz, Germany.
Life 2021, 11(4), 267; https://doi.org/10.3390/life11040267
Submission received: 7 January 2021 / Revised: 12 February 2021 / Accepted: 22 March 2021 / Published: 24 March 2021
(This article belongs to the Special Issue Telomere and Heterochromatin Biology in Ageing and Disease)
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Abstract

Heterochromatic regions render the replication process particularly difficult due to the high level of chromatin compaction and the presence of repeated DNA sequences. In humans, replication through pericentromeric heterochromatin requires the binding of a complex formed by the telomeric factor TRF2 and the helicase RTEL1 in order to relieve topological barriers blocking fork progression. Since TRF2 is known to bind the Origin Replication Complex (ORC), we hypothesized that this factor could also play a role at the replication origins (ORI) of these heterochromatin regions. By performing DNA combing analysis, we found that the ORI density is higher within pericentromeric satellite DNA repeats than within bulk genomic DNA and decreased upon TRF2 downregulation. Moreover, we showed that TRF2 and ORC2 interact in pericentromeric DNA, providing a mechanism by which TRF2 is involved in ORI activity. Altogether, our findings reveal an essential role for TRF2 in pericentromeric heterochromatin replication by regulating both replication initiation and elongation.
Keywords: TRF2; heterochromatin; pericentromeric DNA; ORC; replication; telomeres TRF2; heterochromatin; pericentromeric DNA; ORC; replication; telomeres

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MDPI and ACS Style

Bauwens, S.; Lototska, L.; Koundrioukoff, S.; Debatisse, M.; Ye, J.; Gilson, E.; Mendez-Bermudez, A. The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin. Life 2021, 11, 267. https://doi.org/10.3390/life11040267

AMA Style

Bauwens S, Lototska L, Koundrioukoff S, Debatisse M, Ye J, Gilson E, Mendez-Bermudez A. The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin. Life. 2021; 11(4):267. https://doi.org/10.3390/life11040267

Chicago/Turabian Style

Bauwens, Serge, Liudmyla Lototska, Stephane Koundrioukoff, Michelle Debatisse, Jing Ye, Eric Gilson, and Aaron Mendez-Bermudez. 2021. "The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin" Life 11, no. 4: 267. https://doi.org/10.3390/life11040267

APA Style

Bauwens, S., Lototska, L., Koundrioukoff, S., Debatisse, M., Ye, J., Gilson, E., & Mendez-Bermudez, A. (2021). The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin. Life, 11(4), 267. https://doi.org/10.3390/life11040267

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