DNA Polymerase Delta Synthesizes Both Strands during Break-Induced Replication.

DNA Polymerase Delta Synthesizes Both Strands during Break-Induced Replication.

Donnianni, Roberto A;Zhou, Zhi-Xiong;Lujan, Scott A;Al-Zain, Amr;Garcia, Valerie;Glancy, Eleanor;Burkholder, Adam B;Kunkel, Thomas A;Symington, Lorraine S;
molecular cell 2019
315
donnianni2019dnamolecular

Abstract

Break-induced replication (BIR) is a pathway of homology-directed repair that repairs one-ended DNA breaks, such as those formed at broken replication forks or uncapped telomeres. In contrast to conventional S phase DNA synthesis, BIR proceeds by a migrating D-loop and results in conservative synthesis of the nascent strands. DNA polymerase delta (Pol δ) initiates BIR; however, it is not known whether synthesis of the invading strand switches to a different polymerase or how the complementary strand is synthesized. By using alleles of the replicative DNA polymerases that are permissive for ribonucleotide incorporation, thus generating a signature of their action in the genome that can be identified by hydrolytic end sequencing, we show that Pol δ replicates both the invading and the complementary strand during BIR. In support of this conclusion, we show that depletion of Pol δ from cells reduces BIR, whereas depletion of Pol ε has no effect.

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