DEVELOPMENTAL REGULATION OF MCM REPLICATION FACTORS IN XENOPUS-LAEVIS

At the midblastula transition (MET) during Xenopus laevis development, zygotic transcription begins [1], and the rapid, early cleavage cycle s are replaced by cell-division cycles that lengthen and acquire G (ga p) phases [2] and checkpoints [3-5]. This cell-cycle remodeling may re sult from either a loss of maternal products, the transcription of zyg otic genes, or the replacement of maternal proteins by zygotic gene pr oducts. We have identified an example of the third possibility: distin ct maternal and zygotic genes encoding a member of the minichromosome maintenance (MCM) protein family. The mom genes were identified in yea st by mutations that blocked replication of artificial chromosomes or perturbed the G1/S transition in the cell cycle [6,7]. In Xenopus eggs , the MCM2-MCM7 proteins assemble as multimeric complexes at chromosom al origins of replication [8-14]. The sequential, cell-cycle-dependent assembly of the origin replication complex (ORC), CDC6 protein and th e MCM complex at origins of replication ensures that DNA replicates on ly once per cell cycle [15,16]. The periodic association of the MCM co mplex with chromatin may be regulated via phosphorylation by cyclin de pendent kinases (Cdks) [11]. We have cloned the first example of a dev elopmentally regulated morn gene, zygotic mcm6 (zmcm6), expressed only after gastrulation when the cell cycle is remodeled. The zMCM6 protei n assembles into MCM complexes and differs from maternal MCM6 (mMCM6) in having a carboxy-terminal extension and a consensus cyclin-Cdk phos phorylation site. There may also be maternal-zygotic pairs of other MC Ms. These data suggest that MCMs are critical for cell-cycle remodelin g during early Xenopus development. (C) Current Biology Ltd ISSN 0960- 9822.