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- W3175041727 abstract "ABSTRACT MCM complexes are loaded onto chromosomes to license DNA replication origins in G1 phase of the cell cycle, but it is not yet known how mammalian MCM complexes are adequately distributed to both euchromatin and heterochromatin. To address this question, we combined time-lapse live-cell imaging with fixed cell immunofluorescence imaging of single human cells to quantify the relative rates of MCM loading in heterochromatin and euchromatin at different times within G1. We report here that MCM loading in euchromatin is faster than in heterochromatin in very early G1, but surprisingly, heterochromatin loading accelerates relative to euchromatin loading in middle and late G1. These different loading dynamics require ORCA-dependent differences in ORC distribution during G1. A consequence of heterochromatin origin licensing dynamics is that cells experiencing a truncated G1 phase from premature cyclin E expression enter S phase with under-licensed heterochromatin, and DNA damage accumulates preferentially in heterochromatin in the subsequent S/G2 phase. Thus G1 length is critical for sufficient MCM loading, particularly in heterochromatin, to ensure complete genome duplication and to maintain genome stability." @default.
- W3175041727 created "2021-07-05" @default.
- W3175041727 creator A5048419710 @default.
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- W3175041727 creator A5059574267 @default.
- W3175041727 creator A5061922975 @default.
- W3175041727 creator A5068953744 @default.
- W3175041727 date "2021-06-30" @default.
- W3175041727 modified "2023-10-14" @default.
- W3175041727 title "The consequences of differential origin licensing dynamics in distinct chromatin environments" @default.
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