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


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 ?) 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 ? replicates both the invading and the complementary strand during BIR. In support of this conclusion, we show that depletion of Pol ? from cells reduces BIR, whereas depletion of Pol ? has no effect.

SUBMITTER: Donnianni RA 

PROVIDER: S-EPMC6862718 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Donnianni Roberto A RA   Zhou Zhi-Xiong ZX   Lujan Scott A SA   Al-Zain Amr A   Garcia Valerie V   Glancy Eleanor E   Burkholder Adam B AB   Kunkel Thomas A TA   Symington Lorraine S LS  

Molecular cell 20190905 3


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 st  ...[more]

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