Minimal Resection Takes Place during Break-Induced Replication Repair of Collapsed Replication Forks and Is Controlled by Strand Invasion

TY - JOUR

T1 - Minimal Resection Takes Place during Break-Induced Replication Repair of Collapsed Replication Forks and Is Controlled by Strand Invasion

AU - Jakobsen, Kristoffer P.

AU - Nielsen, Kirstine O.

AU - Løvschal, Katrine V.

AU - Rødgaard, Morten

AU - Andersen, Anni H.

AU - Bjergbæk, Lotte

PY - 2019/1

Y1 - 2019/1

N2 - A natural and frequently occurring replication problem is generated by the action of topoisomerase I (Top1). Trapping of Top1 in a cleavage complex on the DNA generates a protein-linked DNA nick (PDN), which upon DNA replication can be transformed into a one-ended double-strand break (DSB). Break-induced replication (BIR) has been recognized as a critical repair mechanism of one-ended DSBs. Here, we have investigated resection at a one-ended DSB formed exclusively during replication due to Top1-mimicking damage. We show that resection is minimal, and only when strand invasion is abolished is extensive resection detected. When DNA synthesis is slowed by hydroxyurea treatment, extended resection is not observed, which suggests that strand invasion and/or heteroduplex formation restrains resection. Our results demonstrate that the BIR pathway acting during S phase is tailored to prevent hazardous effects of naturally and frequently occurring DNA breaks such as Top1-generated PDNs.

AB - A natural and frequently occurring replication problem is generated by the action of topoisomerase I (Top1). Trapping of Top1 in a cleavage complex on the DNA generates a protein-linked DNA nick (PDN), which upon DNA replication can be transformed into a one-ended double-strand break (DSB). Break-induced replication (BIR) has been recognized as a critical repair mechanism of one-ended DSBs. Here, we have investigated resection at a one-ended DSB formed exclusively during replication due to Top1-mimicking damage. We show that resection is minimal, and only when strand invasion is abolished is extensive resection detected. When DNA synthesis is slowed by hydroxyurea treatment, extended resection is not observed, which suggests that strand invasion and/or heteroduplex formation restrains resection. Our results demonstrate that the BIR pathway acting during S phase is tailored to prevent hazardous effects of naturally and frequently occurring DNA breaks such as Top1-generated PDNs.

KW - break-induced replication

KW - double-strand break repair

KW - resection

KW - topoisomerase-generated damage

KW - BUBBLE

KW - RECOMBINATION

KW - MOBILITY

KW - ARREST

KW - RAD51

KW - SGS1

KW - EXO1

KW - SRS2

KW - DNA TOPOISOMERASES

KW - HELICASE

UR - http://www.scopus.com/inward/record.url?scp=85059862867&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.12.108

DO - 10.1016/j.celrep.2018.12.108

M3 - Journal article

C2 - 30673606

AN - SCOPUS:85059862867

SN - 2211-1247

VL - 26

SP - 836

EP - 844

JO - Cell Reports

JF - Cell Reports

IS - 4

M1 - e3

ER -