Nonreplicative functions of the origin recognition complex

Abstract

Origin recognition complex (ORC), a heteromeric six-subunit complex, is the central component of the eukaryotic pre-replication complex. Recent data from yeast, frogs, flies and mammals present compelling evidence that ORC and its individual subunits have nonreplicative functions as well. The majority of these functions, such as heterochromatin formation, chromosome condensation, and segregation are dependent on ORC-DNA interactions. Furthermore, ORC is involved in the control of cell division via its participation in centrosome duplication and cytokinesis. Recent findings have also demonstrated a direct interaction between ORC and mRNPs and highlighted an essential role of ORC in mRNA nuclear export. Along with the growth of evolutionary complexity of organisms, ORC complex functions become more elaborate and new functions of the ORC sub-complexes and individual subunits have emerged.

A free-living protist that lacks canonical eukaryotic DNA replication and segregation systems

“…1, Supplementary Table 1 ). The lack of these proteins in an eukaryote is unexpected and unprecedented, since their absence would be expected to make the genome prone to DSBs and impair DNA replication, as well as interfere with other non-replicative processes 30 . To rule out false negatives, we conducted further analyses using metamonad-specific HMMs (Hidden Markov Models), various other profile-based search strategies ( Supplementary Information ), tBLASTn 31 searches, and applied HMMER 32 on 6-frame assembly translations.…”

“…Alternatively, SAC-related genes could have been repurposed for another cellular function(s) as in diplomonads 56 . Given that ORC has been observed to interact with the kinetochore (throughout chromosome condensation and segregation), centrioles and promotes cytokinesis 30 , the lack of Ncd80 and ORC complexes suggest that Carpediemonas species possess radically unconventional cell division systems.…”

“…In addition to the aforementioned apparent dysregulation of checkpoint controls in Carpediemonas , alternative mechanisms for chromosome condensation, spindle attachment, sister chromatid cohesion, cytokinesis, heterochromatin formation, and silencing and transcriptional regulation can also be expected in this organism due to the absence of ORC and Cdc6 (reviewed in refs 30, 103, 104 ). All of the absences of canonical eukaryotic systems we have described for Carpediemonas suggest that a radically different cell cycle has evolved in this free-living protistan lineage.…”

Transcriptional Activity of the Bacterial Replication Initiator DnaA

“…In the archaeon Sulfolobus islandicus, replication initiator proteins were shown to bind the promoter regions and regulate the expression of genes involved in DNA damage response (Sun et al, 2018). The ability of replication initiators to regulate gene expression in eukaryotes and archaea are a relatively recent discovery that continues to accumulate supporting data (Popova et al, 2018;Hu et al, 2020).…”

Chromatin Modifiers in Transcriptional Regulation: New Findings and Prospects

“…Совсем недавно показано, что этот комплекс целиком вовлечен в процессинг мРНК и ее транспорт из ядра в цитоплазму. Оказалось, что многие субъединицы ORC взаимодействуют in vivo с факторами процессинга, а их нокдаун приводит к нарушению транспорта мРНК [139,140].…”