TY - JOUR
T1 - A mechanism for Rad53 to couple leading- And lagging-strand DNA synthesis under replication stress in budding yeast
AU - Serra-Cardona, Albert
AU - Yu, Chuanhe
AU - Zhang, Xinmin
AU - Hua, Xu
AU - Yao, Yuan
AU - Zhou, Jiaqi
AU - Gan, Haiyun
AU - Zhang, Zhiguo
N1 - Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/9/21
Y1 - 2021/9/21
N2 - In response to DNA replication stress, DNA replication checkpoint kinase Mec1 phosphorylates Mrc1, which in turn activates Rad53 to prevent the generation of deleterious single-stranded DNA, a process that remains poorly understood. We previously reported that lagging-strand DNA synthesis proceeds farther than leading strand in
rad53-1 mutant cells defective in replication checkpoint under replication stress, resulting in the exposure of long stretches of the leading-strand templates. Here, we show that asymmetric DNA synthesis is also observed in
mec1-100 and
mrc1-AQ cells defective in replication checkpoint but, surprisingly, not in
mrc1∆ cells in which both DNA replication and checkpoint functions of Mrc1 are missing. Furthermore, depletion of either Mrc1 or its partner, Tof1, suppresses the asymmetric DNA synthesis in
rad53-1 mutant cells. Thus, the DNA replication checkpoint pathway couples leading- and lagging-strand DNA synthesis by attenuating the replication function of Mrc1-Tof1 under replication stress.
AB - In response to DNA replication stress, DNA replication checkpoint kinase Mec1 phosphorylates Mrc1, which in turn activates Rad53 to prevent the generation of deleterious single-stranded DNA, a process that remains poorly understood. We previously reported that lagging-strand DNA synthesis proceeds farther than leading strand in
rad53-1 mutant cells defective in replication checkpoint under replication stress, resulting in the exposure of long stretches of the leading-strand templates. Here, we show that asymmetric DNA synthesis is also observed in
mec1-100 and
mrc1-AQ cells defective in replication checkpoint but, surprisingly, not in
mrc1∆ cells in which both DNA replication and checkpoint functions of Mrc1 are missing. Furthermore, depletion of either Mrc1 or its partner, Tof1, suppresses the asymmetric DNA synthesis in
rad53-1 mutant cells. Thus, the DNA replication checkpoint pathway couples leading- and lagging-strand DNA synthesis by attenuating the replication function of Mrc1-Tof1 under replication stress.
KW - Asymmetric DNA synthesis
KW - Deleterious ssDNA
KW - Mrc1
KW - Rad53
KW - Replication stress
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U2 - 10.1073/pnas.2109334118
DO - 10.1073/pnas.2109334118
M3 - Article
C2 - 34531325
AN - SCOPUS:85115273067
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 38
M1 - e2109334118
ER -