REV7 directs DNA repair pathway choice

REV7 is a small multifunctional protein that participates in multiple DNA repair pathways, most notably translesion DNA synthesis and double-strand break (DSB) repair. While the role of REV7 in translesion synthesis has been known for several decades, its function in DSB repair is a recent discovery...

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Vydáno v:	Trends in cell biology Ročník 31; číslo 12; s. 965 - 978
Hlavní autoři:	Clairmont, Connor S., D’Andrea, Alan D.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Ltd 01.12.2021 Elsevier BV
Témata:	ATPases Associated with Diverse Cellular Activities - genetics ATPases Associated with Diverse Cellular Activities - metabolism Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Deoxyribonucleic acid DNA DNA biosynthesis DNA damage DNA Repair DNA Replication Domains Double-strand break repair Fanconi anemia Mad2 Proteins - genetics Mad2 Proteins - metabolism Repair Replication forks REV7 Shieldin Synthesis translesion synthesis TRIP13 Yeast REV7 Fanconi anemia Shieldin double-strand break repair TRIP13 DNA repair translesion synthesis
ISSN:	0962-8924, 1879-3088, 1879-3088
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Popis
Shrnutí:	REV7 is a small multifunctional protein that participates in multiple DNA repair pathways, most notably translesion DNA synthesis and double-strand break (DSB) repair. While the role of REV7 in translesion synthesis has been known for several decades, its function in DSB repair is a recent discovery. Investigations into the DSB repair function of REV7 have led to the discovery of a new DNA repair complex known as Shieldin. Recent studies have also highlighted the importance of REV7’s HORMA domain, an ancient structural motif, in REV7 function and have identified the HORMA regulators, TRIP13 and p31, as novel DNA repair factors. In this review, we discuss these recent findings and their implications for repair pathway choice, at both DSBs and replication forks. We suggest that REV7, in particular the activation state of its HORMA domain, can act as a critical determinant of mutagenic versus error-free repair in multiple contexts. REV7 is a critical component of multiple complexes including well-characterized DNA repair complexes: DNA polymerase ζ and Shieldin, and other poorly understood protein complexes.REV7 is a HORMA family protein, characterized by a distinctive tertiary structure and an associated regulatory mechanism, where activity is controlled by stable conformational changes.The TRIP13 ATPase and p31 regulatory subunit remodel REV7 to the inactive HORMA conformation, inhibiting both polymerase ζ-mediated DNA synthesis and the activity of the Shieldin complex in promoting non-homologous end joining repair.REV7 plays a similar role in both Shieldin and polymerase ζ by connecting the upstream recruitment modules and downstream effector modules when REV7 is in its closed, active conformation.In both Shieldin and polymerase ζ, REV7 promotes the choice of a potentially mutagenic DNA repair pathway over higher fidelity alternatives. We propose that REV7 activity may be a powerful mechanism for a cell to fine-tune the amount of mutagenesis it is willing to tolerate.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	0962-8924 1879-3088 1879-3088
DOI:	10.1016/j.tcb.2021.05.009