PT - JOURNAL ARTICLE AU - Paolo Mita AU - Aleksandra Wudzinska AU - Xiaoji Sun AU - Joshua Andrade AU - Shruti Nayak AU - David J. Kahler AU - Sana Badri AU - John LaCava AU - Beatrix Ueberheide AU - Chi Y. Yun AU - David Fenyo AU - Jef D. Boeke TI - LINE-1 and the cell cycle: protein localization and functional dynamics AID - 10.1101/147587 DP - 2017 Jan 01 TA - bioRxiv PG - 147587 4099 - http://biorxiv.org/content/early/2017/06/30/147587.short 4100 - http://biorxiv.org/content/early/2017/06/30/147587.full AB - LINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology to aid its proliferation. However, a clear understanding of L1’s lifecycle and the processes involved in restricting its insertion and its intragenomic spreading remains elusive. Here we identify modes of L1 proteins’ entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.