Dataset Information

Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3

ABSTRACT: Although Poly(ADP-ribose)-polymerases (PARPs) are key regulators of genome stability, how site-specific ADP-ribosylation regulates DNA repair is unclear. Here, we describe a novel role for PARP1 and PARP2 in regulating Rad52-dependent replication fork repair to maintain cell viability when HR is dysfunctional, suppress replication-associated DNA damage, and maintain genome stability. Mechanistically, Mre11 is required for induction of PARP activity in response to replication stress that in turn promotes break-induced replication (BIR) through assembly of Rad52 at stalled/damaged replication forks. Further, by mapping ADP-ribosylation sites induced upon replication stress, we identify that PolD3 is a target for PARP1/PARP2 and importantly, that its site-specific ADP-ribosylation is required for BIR activity, replication fork recovery and genome stability. Overall, these data identify a critical role for Mre11-dependent PARP activation and site-specific ADP-ribosylation in regulating BIR to maintain genome integrity during DNA synthesis.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Sara Larsen

LAB HEAD: Michael Lund Nielsen

PROVIDER: PXD035661 | Pride | 2023-10-24

REPOSITORIES: Pride

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			Action	DRS
	20200713_LUMOS1_LC6_SCL_SA_collab_ADPr_12h_HU_01.raw	Raw
	20200713_LUMOS1_LC6_SCL_SA_collab_ADPr_12h_HU_02.raw	Raw
	20200713_LUMOS1_LC6_SCL_SA_collab_ADPr_12h_HU_03.raw	Raw
	20200713_LUMOS1_LC6_SCL_SA_collab_ADPr_12h_HU_04.raw	Raw
	20200713_LUMOS1_LC6_SCL_SA_collab_ADPr_16h_HU_01.raw	Raw

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Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3.

Richards Frederick F Llorca-Cardenosa Marta J MJ Langton Jamie J Buch-Larsen Sara C SC Shamkhi Noor F NF Sharma Abhishek Bharadwaj AB Nielsen Michael L ML Lakin Nicholas D ND

Nature communications 20230718 1

Although Poly(ADP-ribose)-polymerases (PARPs) are key regulators of genome stability, how site-specific ADP-ribosylation regulates DNA repair is unclear. Here, we describe a novel role for PARP1 and PARP2 in regulating Rad52-dependent replication fork repair to maintain cell viability when homologous recombination is dysfunctional, suppress replication-associated DNA damage, and maintain genome stability. Mechanistically, Mre11 and ATM are required for induction of PARP activity in response to r ...[more]

PMID: 37463936

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