Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence

Qiming Sun; Toshiki Tsurimoto; Franceline JuillardLin LiShijun LiErika De León VázquezShe ChenKenneth Kaye

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Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence

机译：Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence

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Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp proliferating cell nuclear antigen (PCNA) loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第32期|11816-11821|共6页
作者
Qiming Sun; Toshiki Tsurimoto; Franceline JuillardLin LiShijun LiErika De León VázquezShe ChenKenneth Kaye;
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作者单位

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;

Department of Biology, Kyushu University, Fukuoka 812-8581, Japan;

Proteomics Center, National Institute of Biological Sciences, Beijing 102206, People's Republic of China;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
sarcoma-associated; LANA recruits; DNA polymerase clamp;

Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence

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