The DASH-type Cryptochrome from the Fungus Mucor circinelloides Is a Canonical CPD-Photolyase

Sep 18, 2020Current biology : CB

A light-sensitive protein from the fungus Mucor circinelloides acts as a typical DNA repair enzyme

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Abstract

Cry-DASH from Mucor circinelloides repairs cyclobutane pyrimidine dimers in double-stranded DNA both in vitro and in vivo.

Cry-DASH proteins are a subgroup of cryptochromes that have been linked to DNA repair mechanisms.
Previous studies indicated that cry-DASH can repair lesions in single-stranded DNA but not in double-stranded DNA.
Structural analysis suggests similar features between photolyases and cryptochromes, potentially explaining their functions.
In the fungus Phycomyces blakesleeanus, cry-DASH has shown the ability to repair DNA damage in double-stranded DNA.
The study proposes that M. circinelloides cry-DASH represents an evolutionary shift allowing double-stranded DNA repair.

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Cryptochromes and photolyases are blue-light photoreceptors and DNA-repair enzymes, respectively, with conserved domains and a common ancestry [1-3]. Photolyases use UV-A and blue light to repair lesions in DNA caused by UV radiation, photoreactivation, although cryptochromes have specialized roles ranging from the regulation of photomorphogenesis in plants, to clock function in animals [4-7]. A group of cryptochromes (cry-DASH) [8] from bacteria, plants, and animals has been shown to repair in vitro cyclobutane pyrimidine dimers (CPDs) in single-stranded DNA (ssDNA), but not in double-stranded DNA (dsDNA) [9]. Cry-DASH are evolutionary related to 6-4 photolyases and animal cryptochromes, but their biological role has remained elusive. The analysis of several crystal structures of members of the cryptochrome and photolyase family (CPF) allowed the identification of structural and functional similarities between photolyases and cryptochromes [8, 10-12] and led to the proposal that the absence of dsDNA repair activity in cry-DASH is due to the lack of an efficient flipping of the lesion into the catalytic pocket [13]. However, in the fungus Phycomyces blakesleeanus, cry-DASH has been shown to be capable of repairing CPD lesions in dsDNA as a bona fide photolyase [14]. Here, we show that cry-DASH of a related fungus, Mucor circinelloides, not only repairs CPDs in dsDNA in vitro but is the enzyme responsible for photoreactivation in vivo. A structural model of the M. circinelloides cry-DASH suggests that the capacity to repair lesions in dsDNA is an evolutionary adaptation from an ancestor that only had the capacity to repair lesions in ssDNA.

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The DASH-type Cryptochrome from the Fungus Mucor circinelloides Is a Canonical CPD-Photolyase

Abstract

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